Bob Gibbs knows the importance of cancer research and the life-saving therapies it creates. The 40-year-old husband and father of 4 would not be alive today without these new discoveries and innovations.

	In May 2004, Gibbs was diagnosed with an oligoastrocytoma in his right occipital lobe. Given the low grade of his tumor (grade II), he did not qualify for a clinical trial on a groundbreaking cancer vaccine. His only options were surgery, chemotherapy, and the hope that the tumor would not become more aggressive.

	Gibbs had an initial surgery for removal of a primary brain tumor in 2005, and at that time elected to have only 70% of the tumor removed.

	“I wanted to save my vision,” Gibbs recalled. “I wanted to be able to continue to work and provide for my family.” His surgeon did not agree with the plan to partially remove the tumor because he felt that it would just continue to grow. Undeterred, Gibbs’ primary motivation was to provide for his family, so risking potential blindness was not an option for him. Gibbs said, “I felt that if I could get another five years…to earn income to try to get things paid down, it would set my family up” so that they would be financially secure in the event that he did not survive.

	So, Gibbs had the surgery to debulk the tumor. Then he and his wife, Barb, spent countless hours researching every possible option and every possible treatment, no matter how early in the clinical trial stage it was. Their research led them to UCLA Medical Center, in Los Angeles, California, where researchers were conducting a phase I clinical trial for DCVax (Northwest Biotherapeutics, Inc, Bethesda, MD), an experimental autologous cellular therapy designed to create a specific immune response against a patient’s cancer cells. The problem was that, given the low grade of his tumor, Gibbs did not yet qualify for the trial.

	Making matters worse, 1 year after Gibbs’ initial diagnosis, his 13-year old son was diagnosed with a brain tumor. “We were hit within 363 days of each other,” Gibbs said. “The challenge went from saving my life to trying to save my life and the life of my oldest son.”

	Fortunately, his son’s tumor was a vascular type of malformation in the brain and was not cancerous. However, Gibbs’ tumor continued to grow and had progressed into a grade III tumor. This was both bad and good. The advanced tumor stage meant the disease was progressing, however, the grade III tumor had qualified him for the DCVax clinical trial at UCLA.

	Both Gibbs and his wife felt that it was ridiculous that patients with brain tumors had to wait for cancer to become more aggressive—to the point at which it could potentially shorten their lives&mdash;before qualifying for cutting-edge treatments. “If the vaccine had been available to me…following the first surgery [in 2004], things could have turned out so much differently,” Gibbs said.

	Four years later, Gibbs and his wife were at their home in Clearwater, Florida. At the time, Gibbs was recovering from his second surgery in 3 years for removal of the brain tumor. Born blind in his left eye, the second surgery left him with only partial vision in his right eye. “I can’t drive, and I’m unable to work,” Gibbs complained. He was outwardly frustrated and depressed.

	“This negativity is [getting me] nowhere,” Gibbs said to Barb. “I’ve got to do something.” That drive helped Gibbs and his wife establish 

, a nonprofit organization to raise national awareness and funding for cutting-edge cancer research. Getting to that point, however, was no easy ride.

	Not wanting to see other patients with brain tumors be denied access to treatments that could make a difference in combating their disease, Gibbs and his wife were determined to bring about a change. They organized the 

 charity bicycle ride in September 2008. Gibbs noted that, with the exception of their wedding, he and Barb had never organized anything on the scale of this bike ride. Afterward, as they went through the donations, they noticed that several of the checks were made out to 

, the name of the event, instead of the research center, UCLA. They were left with two choices: contact the dozens of people who had written the checks or start a nonprofit organization called 

	“We wanted to fund cutting-edge research,” Gibbs explained. “The biggest thing in dealing with cancer is hanging on to hope that you’re going to survive, that you’re going to find a good treatment.” He pointed out that patients with brain tumors encounter many financial hardships; most focus on the cost of visits to radiation oncologists and neurosurgeons, and chemotherapy copayments, but many tend to overlook the costs associated with transportation to and from the clinical trial sites.

	Gibbs said, “We wanted to provide travel assistance so that people could get to these clinical trials, because most of the time [patients with brain tumors] are left financially devastated.” As for his own travel expenses, he added, “If it weren’t for family and friends having the ability to help us with frequent flyer miles, we could never have made multiple trips out to UCLA.”

 has become “the little engine that could.” From that first bicycle ride in 2008, the organization now has 10 different events scheduled in 2011 in cities across the country.

	Gibbs recalled that it was the thought of his children being without a father that initially drove him to find an acceptable treatment option for his brain tumor. While that has not changed, he is also driven by the people he hears from on a regular basis. “So many people tell me, ‘You’re an inspiration. You give me hope that I can survive, too,’” Gibbs said.

	Unfortunately, Gibbs’ tumor has continued to grow. He had gone 2 years without any signs of growth, but a recent MRI uncovered a recurrence. “We were able to catch it early,” he explained, “and I’m back on the vaccine now, as well as chemotherapy. Other than the side effects of the chemotherapy, I feel fine.”

	Even as he battles his own health issues, Gibbs manages to remain in good spirits, and somehow maintains a sense of humor despite his present condition. “Every time I make my wife angry, she goes over to my left side and just makes faces, because she knows I can’t see her,” Gibbs explains, laughing. He also continues to work tirelessly to raise awareness and funding for cutting-edge research and clinical trials, and to provide patients with travel assistance. He acknowledges that progress is being made, but he admits that he expects more.

	“One thing you have to understand about me is I expect more than I’m able to sometimes physically achieve as one person, or one organization,” Gibbs admitted. “As we see patients continually being diagnosed, patients losing their lives, friends we’ve met, it doesn’t seem like we’re moving fast enough. But, we are making progress. And one day, we’ll be there.”

Articles

Miles for Hope: Cancer Survivor Works to Raise Awareness and Funding for Brain Tumor Research

	The aggressive peripheral T-cell lymphomas make up less than 10% of all lymphomas diagnosed each year in the United States. They provide a wide variety of clinical syndromes, many of which have been well defined only in the past few decades. The results of therapy for patients with aggressive peripheral T-cell lymphomas have been much worse than observed for patients with aggressive B-cell lymphomas. This undoubtedly reflects, at least in part, that only a minority of patients with aggressive peripheral T-cell lymphoma are included in clinical trials. It is not surprising that the most effective therapy for diffuse large B-cell lymphoma—the most common of the aggressive lymphomas&mdash;was the most effective treatment in these trials. Since peripheral T-cell lymphomas are clinically and biologically distinct entities, there would have been no reason to expect that the same treatment would work equally for them.

	The aggressive peripheral T-cell lymphomas, despite their relative infrequency, include a wide variety of illnesses (

 These tumors can be subdivided into those developing primarily in (1) lymph nodes and (2) extranodal sites. The subtypes of aggressive peripheral T-cell lymphomas will be dealt with in the rest of this paper, and are divided into those of primary nodal and primary extranodal origin.

	The ability of pathologists to diagnose aggressive peripheral T-cell lymphoma has been much less reproducible than their ability to diagnose aggressive B-cell lymphomas. For example, expert hematopathologists using modern classification systems are able to diagnose aggressive B-cell lymphomas, with few exceptions, in a highly reproducible manner.

 However, a recent study of the WHO classification system for the aggressive T-cell lymphomas found an approximately 10% lower rate of agreement by expert hematopathologists than was seen for B-cell lymphomas (

 The application of gene expression studies has the potential to improve our ability to diagnose aggressive peripheral T-cell lymphomas. A recent review suggested that gene expression patterns will have an impact on our ability to classify aggressive peripheral T-cell lymphomas and are likely to be particularly important with certain subtypes.

 For example, it appears that angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma, and adult T-cell leukemia/lymphoma have robust and reproducible molecular signatures.

 In contrast, peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) was molecularly heterogeneous, with some tumors showing the molecular signature of angioimmunoblastic T-cell lymphoma.

 PRIMARILY NODAL AGGRESSIVE PERIPHERAL T-CELL LYMPHOMAS

 Peripheral T-Cell Lymphoma Not Otherwise Specified

	Patients with PTCL-NOS present at a median age of 60 years with a striking male predominance (

). About 70% of patients will have widespread disease. The distinction between these patients and those with diffuse large B-cell lymphoma can be made on biopsy only when the tumor cells mark as mature T-cells. Unfortunately, the treatment outcome for patients with PTCL-NOS has been much poorer, with shorter survival and one-third to one-fourth the chance to remain free of disease for 5 years.

	We now know that not all tumors with a PTCL-NOS diagnosis are the same. Some of them have gene expression patterns characteristic of angioimmunoblastic T-cell lymphoma.

 There appears to be more than one other subgroup, though these are not yet well defined. It obviously confounds the interpretation of clinical trials and suggests that not all patients will benefit maximally from the same treatment.

	The most common treatment for patients with PTCL-NOS has been an anthracycline-containing regimen like cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Because of the poor results seen to date, many physicians offer an autologous transplant in first remission, although it is unclear that this yields a significant advantage. A number of new drugs are being studied in these patients (

), although none have yet made it into first-line therapy. For patients with aggressive peripheral T-cell lymphomas, we are in desperate need of an improved treatment regimen that could serve as a standard in the same way that CHOP has for patients with diffuse large B-cell lymphoma. For patients who relapse, both autologous and allogeneic hematopoietic stem cell transplantation can be curative.

 At least one report suggested that for patients with recurrent disease, allogeneic transplantation is superior.

	Angioimmunoblastic T-cell lymphoma is the second most common of the aggressive peripheral T-cell lymphomas.

 It occurs more frequently in northern Europe.

 The typical patient with this tumor is aged >60 years, presents with systemic symptoms, and has widespread disease and an elevated level of lactate dehydrogenase. As might be expected, survival has been poor, with a large international review

 showing a 5-year failure-free rate of 18% and a 5-year overall rate of 32%.

	The optimal treatment for patients with angioimmunoblastic T-cell lymphoma is not certain. Only a minority of patients will benefit in the long term from traditional anthracycline-based therapy. New treatment approaches have included the addition of alemtuzumab to a CHOP-like regimen and the use of early autologous hematopoietic stem cell transplantation. A small series that combined CHOP with alemtuzumab had a high rate of complete remission.

 Autologous hematopoietic stem cell  transplantation can induce long-term disease-free survival and is most likely to be effective when patients are transplanted in complete remission.

 A series using allogeneic hematopoietic stem cell transplantation for patients with relapsed angioimmunoblastic T-cell lymphoma showed that either myeloablative or reduced-intensity allogeneic transplantation can produce long-term disease-free survival.

	A variety of other treatments have been utilized in patients with angioimmunoblastic T-cell lymphoma. One report showed that some patients responded to cyclosporine and obtained a complete response with maintenance cyclosporine.

 In addition, a small report suggested that combining rituximab with the CHOP regimen might benefit patients with angioimmunoblastic T-cell lymphoma—perhaps by eliminating CD20-positive cells and interfering with intercellular signaling.

	The tumors that we now call anaplastic large cell lymphoma are characterized pathologically by large anaplastic cells that like carcinomas tend to grow cohesively and frequently invade lymph node sinuses. As a result, these tumors were frequently misclassified as undifferentiated carcinomas, malignant melanomas, or malignant histiocytosis until the discovery in 1985 of the Ki-1 (now CD30) marker.

 CD30 was known to be a marker for Reed-Sternberg cells, but this led to the discovery of anaplastic large cell lymphoma, which uniformly expresses CD30. (A cutaneous variant of anaplastic large cell lymphoma has a much less aggressive course and will not be dealt with in this section.

	The ALK gene on chromosome 2 is fused with the nucleophosmin gene on chromosome 5 in the t(2;5) translocation that characterizes a subset of anaplastic large cell lymphomas.

 Patients whose anaplastic large cell lymphomas overexpress the ALK protein and have the characteristic translocation are younger and have a better survival.

 It is not completely clear whether the expression of ALK or the younger age of the ALK-positive patients is the major factor in determining their better outcome.

	In a recent international study, patients with ALKpositive anaplastic large cell lymphoma had a median age of 34 years, in contrast to 58 years in those whose tumors were ALK negative. Males predominated in both groups, and 35% to 40% of patients had stage I or II disease.

 Five-year failure-free survival was 60% in ALK-positive patients and 36% in ALK-negative patients (Table 3), with the International Prognostic Index Score

	Patients with anaplastic large cell lymphoma have the best treatment outcomes among patients with any of the aggressive peripheral T-cell lymphomas. However, the optimal therapy remains uncertain. Treatment has usually included the CHOP regimen, which remains the standard approach for most physicians. Although patients with relapsed peripheral T-cell lymphoma often benefit from autologous bone marrow transplantation, this treatment is not widely included as part of primary therapy. A number of trials are being conducted of antibodies, including those against CD52, CD25, and CD30. In some patients, alemtuzumab has been combined with CHOP.

 SGN-30 and SGN-35 have both been shown to be active in relapsed anaplastic large cell lymphoma,

 with some complete responses. It is unclear whether this approach will benefit patients in combination with standard chemotherapy as the initial treatment.

	Adult T-cell leukemia/lymphoma is one result of infection by the virus HTLV-1. While infection is asymptomatic in most patients, adult-cell leukemia/lymphoma occurs in about 3% of patients. The ensuing syndrome can be predominantly a leukemia or lymphoma, and the clinical course can be smoldering, chronic, or acute.

 Most patients present with disseminated disease and have an aggressive course. This disease is seen most frequently in southern Japan and the Caribbean but can be found throughout the world. The infection can be passed vertically from mother to child or spread through blood products. The management of patients with adult T-cell leukemia/lymphoma is difficult, and most patients presenting with the acute form have a short survival. Patients frequently respond to a variety of chemotherapy regimens but rarely have long-term disease-free survival. There is some evidence that more intensive regimens, including transplantation, are more beneficial.

 PRIMARILY EXTRANODAL AGGRESSIVE PERIPHERAL T-CELL LYMPHOMAS

 Extranodal Natural Killer/T-Cell Lymphomas

	Most natural killer (NK)/T-cell lymphomas present in the nose and nasal sinuses and are termed nasal NK/Tcell lymphoma in the WHO classification. These are the tumors that were once included in the category of lethal midline granuloma, which was not known to be a cancer but was responsive to radiotherapy. Other NK/T-cell lymphomas can present involving other sites in the body and are referred to as extranasal NK/T-cell lymphomas in the WHO classification. Lymphomas presenting in the nose and nasal sinuses are more likely to be localized (73% vs 32%) and have a better 5-year survival (45% vs 10%) than those presenting in other sites.

	Nasal NK/T-cell lymphomas are seen most frequently in Southeast Asia, Korea, and parts of Latin America. In the United States, immigrants from those areas represent a significant proportion of the cases. The presenting symptoms for nasal NK/T-cell lymphomas are usually reflective of the localized nature of the disease. A minority of the patients have systemic symptoms.

 This is an aggressive lymphoma, and patients must be evaluated and treated promptly. When staging evaluation shows evidence of disseminated disease, the chances for cure become greatly diminished.

	Therapy for nasal NK/T-cell lymphoma has been the subject of debate. For patients with localized disease, radiotherapy seems to be the most important component of therapy and is necessary for cure.

 This may be one of the unusual situations in treating lymphomas where radiotherapy should be administered before chemotherapy, though there is no consensus on this point. For example, some clinicians favor the use of radiotherapy alone for localized disease.

 At least one report suggested that concurrent chemotherapy along with radiation, in a manner similar to what is used in some carcinomas, might benefit patients with this disorder.

	Patients who have disease that presents in other sites, or disseminated nasal NK/T-cell lymphoma, have a much poorer outlook. Although most patients will respond at least transiently to chemotherapy, cure is uncommon. There are reports of activity of methotrexate and L-asparaginase, and there are hints that their inclusion in treatment might improve outcomes.

 Some patients have been reported to benefit from autologous and allogeneic hematopoietic stem cell transplantation.

Enteropathy Type Peripheral T-Cell Lymphomas

	Enteropathy-associated T-cell lymphoma is a rare lymphoma that arises in the small intestine; patients usually present with abdominal pain and weight loss. People with celiac disease seem to be at higher risk for this disorder.

 Note, however, that many patients with this disorder do not have a history of celiac disease and that lymphomas of the small intestine in patients with celiac disease can also be diffuse large B-cell lymphoma.

	Patients with enteropathy-associated T-cell lymphoma have a poor survival rate (Table 3). They are often very ill by the time of diagnosis, and intestinal perforation is not uncommon at presentation. These poor presenting characteristics often limit treatment options. Patients are often treated initially with surgery, but it rarely yields long-term disease-free survival. Anthracycline-based chemotherapy regimens have poor outcomes, with many patients unable to tolerate a full course of therapy.

 However, a recent report of intensive chemotherapy followed by autologous hematopoietic stem cell transplantation in patients healthy enough to tolerate this approach showed a much better outcome than previously seen. About 50% of patients survived 3 years free of disease,

 in contrast to 5-year failure-free survival of 4% in a large international study that utilized several different treatment approaches.

	Hepatosplenic T-cell lymphoma is a rare disease that typically presents with systemic symptoms such as fevers, night sweats, and malaise combined with liver and spleen enlargement and peripheral blood cytopenias. The initial clinical impression is often of an infectious disease, and the diagnosis of lymphoma is sometimes not made until autopsy—if at all. These patients typically do not have lymphadenopathy, and the tumor cells usually have a sinusoidal growth pattern, which makes pathological diagnosis difficult. The first description of the disease might be a 1990 report of 2 patients who briefly responded to therapy and then died. Unfortunately, the treatment options for these patients have not improved much in recent years.

	Most hepatosplenic T-cell lymphomas display the gamma/delta T-cell receptor rather than the alpha/beta T-cell receptor. It may be that tumors expressing the latter have a somewhat better prognosis. Finding a T-cell gene rearrangement is sometimes the key to diagnosis. Familiarity with the disease, as well as a high degree of suspicion on the part of both clinician and pathologist, increases the likelihood of timely diagnosis.

	Unfortunately, hepatosplenic T-cell lymphoma continues to have a dismal survival rate. In a large international study of T-cell lymphomas, 5-year overall survival was only 7% (Table 3).3 CHOP-based therapies often yield a response, but it is usually transient. Patients have been reported to benefit from alemtuzumab, pentostatin, and fludarabine, but the only therapy that appears to be curative is allogeneic bone marrow transplantation.

Subcutaneous Panniculitis-Like Peripheral

	Subcutaneous panniculitis-like T-cell lymphoma is usually included among the aggressive peripheral T-cell lymphomas. However, a recent report3 of a large number of patients with T-cell lymphomas from around the world showed that patients with this disorder have a much more indolent course than might have been expected. It does appear that patients with the gamma/delta subtype of subcutaneous panniculitis-like T-cell lymphoma do have a more aggressive course than those whose tumors express the alpha/beta T-cell receptor.

 It is likely that many patients with subcutaneous panniculitis-like peripheral T-cell lymphoma are followed for much of their clinical course by dermatologists and are seen by oncologists only when they develop systemic disease.

	The optimal treatment for patients with subcutaneous panniculitis-like T-cell lymphoma is uncertain. Radiotherapy is extremely effective for sites of disease to which it can be applied. Combination chemotherapy regimens such as CHOP can yield remissions, but the chance of remaining in remission for 5 years was only 4%3 (Table 3). Some patients might benefit from autologous or allogeneic hematopoietic stem cell transplantation.

	Aggressive peripheral T-cell lymphomas represent a wide variety of clinical syndromes. However, they are diseases that practicing oncologists will occasionally see. To maximize the chances that patients will benefit from effective therapies, it is important that clinicians be acquainted with these diseases and be aware of treatment advances as they occur. Currently, major lymphoma study groups are focusing on identifying improved treatments for patients with these disorders. There is every reason to believe that the outcome of this work will be a significant improvement in survival—perhaps approaching that seen for patients with the aggressive B-cell lymphomas.

The aggressive peripheral T-cell lymphomas make up less than 10% of all lymphomas diagnosed each year in the United States.

The Aggressive Peripheral T-Cell Lymphomas

	In May 2005, a 25-year-old female presented to her primary care physician complaining of a newly palpable breast mass that had grown to several centimeters over the course of a few months. A mammogram and ultrasound revealed a 3.6 x 3.4 cm left breast mass with several enlarged and suspicious lymph nodes. Adjacent soft tissue masses in the left axilla were deemed suspicious, ranging in size from 1 to 2 cm each. An ultrasound-guided core biopsy of the breast mass revealed a grade 3/3 infiltrating ductal carcinoma that was estrogen receptor/progesterone receptor (ER/PR) positive and HER2/neu 3 (ie, strongly positive). In June 2005, the patient began neoadjuvant chemotherapy with 4 treatments of dose-dense Adriamycin (doxorubicin) and Cytoxan (cyclophosphamide), followed by 2 cycles of Taxol (paclitaxel). Due to the development of severe peripheral neuropathy, her treatment regimen was changed to 2 cycles of Taxotere (docetaxel).

	The patient completed neoadjuvant chemotherapy in November 2005 and underwent a left modified radical mastectomy, with the final pathology revealing a grade 3/3 infiltrating ductal carcinoma that was 3.2 cm, with associated high-grade comedo-type ductal carcinoma in situ (DCIS). All surgical margins were negative, and final pathology revealed a single lymph node involved with metastatic breast cancer. No reconstruction was performed at that time. She recovered from her operation and then received left chest wall radiation followed by adjuvant tamoxifen and trastuzumab therapy. Deemed responsible for an asymptomatic decrease in her ejection fraction, the trastuzumab was subsequently held for 3 months. Her ejection fraction returned to normal; further investigation showed that the decrease was not due to the trastuzumab, but rather the Adriamycin and possibly the adjuvant chest wall radiation. Trastuzumab was restarted in August 2006 and completed in October 2006, and her last ejection fraction was found to be within normal limits.

	In November 2006, the patient developed new-onset midsternal pain that she described as constant and unrelenting. Analgesics and narcotics were required to achieve adequate pain control. A whole-body position emission tomography-computed tomography (PET/CT) scan revealed an area of intense hypermetabolic activity within the central and distal portion of the sternum, extending to and including the xiphoid process (

). This area was described as an expansile lytic lesion of the sternum with large areas of cortical bone destruction. A bone scan was otherwise negative. Her pain continued to increase in severity and her tamoxifen was discontinued. She was started on anastrazole, an aromatase inhibitor, and leuprolide therapy in an attempt to inhibit further growth of this likely sternal metastasis.

	In March 2007, we proceeded with surgical intervention in collaboration with our cardiothoracic and plastic surgery colleagues. We began with a midsternal skin incision followed by a complete 360-degree circumferential dissection of the mid-distal sternum. This left the manubrium and sternal notch intact as the superior aspect of the sternum was clearly uninvolved on imaging studies. A circumferential margin of 3 to 4 cm was removed with resection of the ribs. The central and distal portions of the sternum, including the xiphoid process (

), were also completely removed. Chest wall stability was maintained by leaving the uninvolved superior aspect of the sternum intact. A high-grade adenocarcinoma, which involved bone and periosseous soft tissue consistent with a mammary duct primary cancer, was revealed in a final histologic analysis of the specimen. All rib margins were negative, with the carcinoma closely approximating the deep soft-tissue margin of the surgical resection to within 0.1 mm (

). We had decided preoperatively against placing synthetic mesh or nonautologous tissue into the resulting defect due to the uncertainty of surrounding tissue involvement and the possibility of developing recurrent disease in this area. Thus, the resulting defect measured 13 x 13 cm, and tissue reconstruction was achieved with bilateral pectoralis major muscle advancement flaps brought to the sternal midline, with the vascular pedicle based upon the thoracoacromial artery (

	Following a full recovery from her operation, the patient was again placed on anastrazole and leuprolide, and she has since completed a full year of trastuzumab therapy. She tested negative for BRCA1 and BRCA2 genetic mutations. Despite these negative genetic testing results, she wished to undergo a prophylactic mastectomy of the right breast with immediate bilateral reconstruction. In January 2008, she underwent a right breast prophylactic mastectomy, sentinel lymph node mapping of the right axilla using blue dye only, and the immediate placement of tissue expanders. Due to the patient’s prior course of radiation to the left chest wall, a left latissimus dorsi myocutaneous flap was used for reconstruction and bilateral silicone implants were inserted (

	The final pathology revealed multifocal, high-grade DCIS, intermixed areas of lobular carcinoma in situ (LCIS), and sentinel lymph nodes negative for metastatic cancer. No invasive component was identified. Interestingly, her right breast mammogram never identified an area of abnormality throughout this process. She currently continues on an aromatase inhibition and goserelin therapy every 3 months. A follow-up examination in August 2010 revealed no evidence of disease recurrence. Her recent  whole-body PET/CT scan remains negative for metastatic disease.

	The development of a solitary sternal metastasis in patients with a previous history of breast cancer is rare and represents less than 2% of all cases.1,2 Several authors note that long-term survival can be achieved with either partial or complete sternal resection (also called sternectomy) for an isolated metastasis, with a median survival of ~30 months and a 5-year overall survival of ~60%.

 There are several interesting features in this case report of a woman who developed an aggressive breast cancer at a relatively young age. Her initial diagnosis was at age 25, when she felt a growing mass in her left breast. Subsequently, she was found to have an aggressive, high-grade infiltrating ductal carcinoma with nodal involvement. She appropriately received neoadjuvant chemotherapy and underwent a modified radical mastectomy. The mass recurred as an isolated sternal metastasis within 12 months of this surgery and within 18 months of the original diagnosis of cancer in her left breast. Prophylactic right breast mastectomy revealed high-grade, multifocal DCIS with intermixed areas of LCIS. Genetic testing for BRCA1 and BRCA2 was negative.

	This is a single case in which a primary breast cancer metastasized to the sternum without apparent metastases to other solid organs or other sites of the body. Wedin and colleagues

 described the occurrence of symptomatic bone metastases in a defined population of patients with breast cancer. They identified all patients in the Stockholm Breast Cancer Database (population base 1.8 million) with a diagnosis of bone metastases from 1989 to 1994 and found a total of 641 cases of symptomatic skeletal metastasis, of which 107 (17%) were operated on. Metastases were located in long bones (77), spine (14), and pelvis (6), but none to the sternum. The median survival was 6 years after the initial diagnosis of breast cancer and 2 years after the first recurrence. The median survival from diagnosis of bone metastases was 22 months for patients with bone as the first site of metastases, 15 months for those with locoregional recurrence, and 12 months for those with soft tissue or multiple sites of recurrence.

 reported on 10 patients who received sternal resections for breast cancer recurrence. They further described various techniques of sternal resection followed by immediate tissue reconstruction with or without synthetic material. They noted a 5-year survival of 33%, with a partial resection of the sternum being well tolerated. In addition, hospitalization was short, morbidity was minimal, and local control was excellent. Lequaglie and colleagues

 reported on 88 patients who underwent sternal resections, of which 28 were for metastatic lesions from primary breast cancer. They found a similar 5-year overall survival of 41.8%, and noted that sternal resection followed by plastic reconstruction is a safe, effective treatment option that improves quality of life and can result in long-term survival.

 more specifically performed an in-depth analysis of patients with metastatic breast cancer to clarify whether solitary skeletal metastasis has clinical significance compared with multiple skeletal metastases. They examined 703 patients who developed metastatic bone lesions after beginning treatment for their breast cancer, and further subdivided them into those who had solitary (41%) or multiple (59%) metastatic bone lesions. Of those with solitary metastases, the highest incidence involved the sternum (98 of 289; 34%), while other skeletal sites were more prevalent in patients who had multiple metastatic lesions (

 <.001). Interestingly, they showed that an isolated sternal lesion remains a sole site of metastasis significantly longer than other solitary skeletal metastatic bone lesions. Finally, those patients with a solitary bony metastasis lived significantly longer than those with multiple metastatic bone lesions. This provides additional evidence that a solitary metastatic bone lesion is an independent, favorable prognostic factor in breast cancer patients with skeletal metastasis.

 published a series of 11 patients—4 of whom had recurrent breast cancer&mdash;who underwent sternal tumor resection and immediate chest wall repair with both primary and metastatic tumors. All underwent sternal and partial rib resection and immediate reconstruction with either polytetrafluoroethylene (PTFE) and/or a sandwich of polypropylene with a pedicled musculocutaneous flap. Four of the 5 patients underwent curative surgical intent and the overall survival ranged from 5 to 58 months.

 describe a similar case of a patient who underwent a left modified radical mastectomy for breast cancer and developed a solitary metastatic lesion within the sternal body 4.5 years after her original operation. The patient received radiation therapy and the lesion recurred after 18 months; it was then treated with oral chemotherapy, but the lesion returned 15 months later. At that point, surgical resection was undertaken and a “no-touch” technique was used that involved partial rib removal with 2-cm margins. Reconstruction was completed with a prosthetic chest wall created from methyl methacrylate (MMA) sandwiched between 2 layers of Prolene mesh. The investigators also concluded that excellent local control along with long-term survival is achieved in select cases.

 performed a 25-year retrospective study examining long-term outcomes of 68 patients who underwent a sternectomy for recurrent breast cancer (17 of 68 patients). They found a 5-year overall survival of 37%, which was well within the range of other studies cited. Careful patient selection is important when such cases are approached for curative intent, with palliative resection reserved for those with large, painful lesions. The authors also stressed the role of the multidisciplinary team for optimal medical and surgical outcomes.

	This is a report on a single case of a patient who developed a solitary sternal metastasis following a modified radical mastectomy for a high-grade infiltrating ductal carcinoma of the breast. She underwent a partial sternectomy with 4-cm resection margins followed by immediate reconstruction with bilateral pectoralis muscle advancement flaps to the midline. No synthetic material or mesh was used. The patient fully recovered and has since undergone a second operation with a prophylactic right breast mastectomy with insertion of bilateral tissue expanders followed by breast implants. She has completed her trastuzumab therapy and is more than 5 years from her original diagnosis of breast cancer and more than 3 years from her partial sternectomy. She is currently without evidence of recurrent or distant metastatic disease.

In May 2005, a 25-year-old female presented to her primary care physician complaining of a newly palpable breast mass that had grown to several centimeters over the course of a few months.

Resection and Reconstruction of a Solitary Sternal Metastasis After Mastectomy for Breast Cancer: A Case Report and Review of the Literature

 have evaluated racial/ethnic and age disparities in whether patients receive chemotherapy for nonmetastatic colo-rectal cancer (CRC) treatment and have found that patients of nonwhite race/ethnicity and older patients are less likely to receive chemotherapy. However, these studies did not evaluate specific types of chemotherapy agents used.

	Management of metastatic (stage IV) CRC historically has involved 5-fluorouracil—leucovorin as the standard chemotherapy,

 but the introduction of various novel add-on chemotherapies with improved efficacy has led to an increase in the chemotherapeutic options available to manage stage IV CRC.

 Irinotecan hydrochloride, approved in 1998 as a second-line agent for metastatic CRC treatment and approved in 2000 as a first-line agent for use with 5-fluorouracil—leucovorin,

 was the first of these novel agents to show improved efficacy relative to 5-fluorouracil—leucovorin alone.

 Irinotecan inhibits the enzyme necessary for the reversible breakage and relegation of DNA strands during DNA synthesis, leading to significant improvement in tumor progression slowing and median survival time (approximately 3 additional months relative to the 5-fluorouracil—leucovorin regimen).

 Its availability, as well as the subsequent availability of other novel agents such as oxaliplatin, bevacizumab, and cetuximab, has raised expectations for more efficacious regimens than 5-fluorouracil—leucovorin alone.

 Nevertheless, these novel agents also place patients at higher risk of experiencing adverse effects as a result of their increased toxic effects.

	Knowledge is scarce about racial/ethnic and age disparities in the receipt of newer chemotherapies. Addressing this gap by examining the first of the newer agents marketed for treatment of advanced CRC disease can provide an understanding of healthcare disparities among specific services for CRC management. In addition to knowing whether patients are receiving chemotherapy in real-world settings, it is important to know whether newer chemotherapies are being selectively utilized among chemotherapy users, particularly elderly patients in whom incidence of the disease is high.

	This study sought to determine whether racial/ethnic and age disparities existed in the selection of specific types of chemotherapy among elderly patients with stage IV CRC. Given that irinotecan was the first novel agent to be available at the start of the study period, newer therapy was designated as irinotecan-containing chemotherapy. It was hypothesized that patients of African American race/ethnicity and older patients with stage IV CRC would have a lower likelihood of receipt of newer chemotherapy than white patients and younger patients.

	The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used for this study.

 SEER data provided clinical and demographic information about patients with cancer from SEER registries across the following 16 geographic areas: Connecticut, Detroit (Michigan), Hawaii, Iowa, New Mexico, Seattle (Washington), Utah, Atlanta (Georgia), rural Georgia, Kentucky, Louisiana, New Jersey, greater California, and Los Angeles, San Jose, and San Francisco (California). Health utilization information for these patients was obtained from their Medicare Part A and Part B claims, which include hospital services, physician and other noninstitutional provider services, and outpatient institutional providers.

	A total of 112,345 patients with at least 1 diagnosis of nonappendiceal colon or rectal cancer occurring between 1998 and 2002 were initially identified from SEER. Patients diagnosed at death were excluded (n = 1104 patients), as were patients diagnosed as having nonadenocarcinomas or a stage of disease that did not require any chemotherapy treatment (n = 39,755). Patients younger than 66 years also were excluded to allow a complete year of data during the year before CRC diagnosis to identify prediagnosis comorbidities (n = 10,600).

	Patients who were ineligible for Medicare fee for service were excluded, as were those with no utilization information because of death or loss of Medicare eligibility occurring during the same month of diagnosis (n = 22,140). To ensure that chemotherapy use was specifically for stage IV CRC, patients with a history of cancer dating 5 years or earlier before the current CRC diagnosis or patients with a concurrent cancer occurring in the same year as the CRC diagnosis were excluded (n = 3883). The final sample was further refined to those eligible to receive first-line irinotecan-containing chemotherapy (ie, patients with stage IV disease diagnosed after 1999 [n = 5068]).

	The main variable of interest was the receipt of newer chemotherapy (irinotecan vs all other chemotherapy) within 2 months of chemotherapy initiation. Chemotherapy administration was identified through specific chemotherapy-related medical codes in physician, outpatient facility, and durable medical equipment Medicare claims. Various resources and published studies

 that have measured chemotherapy through Medicare claims were used to identify the relevant codes that represented chemotherapy use. These codes are listed in 

	Patients with any chemotherapy-related Medicare claim were identified as chemotherapy users, and the earliest chemotherapy-related claim on or after the first day of the diagnosis month was used to identify the chemotherapy start date. A 2-month window beginning on the chemotherapy start date was searched for any claims indicating irinotecan use (Healthcare Common Procedure Coding System code J9206). If no irinotecan claims were identified, the chemotherapy user was identified as having received “other” chemotherapy.

SEER-Medicare data were used to identify several clinical variables. Year of diagnosis was obtained from the SEER file. Other SEER clinical variables included a history of cancer that occurred at least 5 years before the cancer diagnosis under study. Furthermore, although all patients had stage IV disease, variability in tumor characteristics such as tumor site and lymph node involvement was observed, and these variables were included in the descriptive analysis.

	The Charlson Comorbidity Index (CCI), a measure of disease burden, was used as a proxy for health status (prediagnosis). The index has been validated as a reliable tool for the prediction of morbidity in patients with cancer.

 Calculation of the index involved using physician and hospital claims in the year preceding cancer diagnosis to search medical codes that reflected the following: myocardial infarction, congestive heart failure, peripheral vascular disease, chronic obstructive pulmonary disease, dementia, paralysis, diabetes, chronic renal failure, liver disease, ulcers, rheumatoid arthritis, and AIDS.

 Because few patients had CCI scores exceeding 2, the final CCI obtained was used to categorize patients into the following 3 groups: 0 CCI, 1 CCI, or more than 1 CCI.

	Other cancer-related procedures occurring within the first 4 months of diagnosis were measured. Codes reflecting surgery to the colorectal region, surgery to metastatic sites (eg, liver, lung), and radiation therapy were identified from published resources (Table 1).

In addition to age at diagnosis and race/ethnicity, sex and marital status were obtained from the SEER-Medicare enrollment files. The following 4 age groups were created: 66 to 70, 71 to 75, 76 to 80, or older than 80 years. Race/ethnicity was categorized as white, African American, or other. A variable indicating whether the patient was married at the time of diagnosis was also available. Finally, SEER registry geographic information was available as a demographic variable.

 Individual-level socioeconomic variables were unavailable. However, SEER data contained a group of aggregate zip code—level and census tract–level household income variables that were used to create a proxy variable for socioeconomic status.37 A compound median household income proxy variable for socioeconomic status was generated using an algorithm previously applied to SEER-Medicare data.38,39 In order of priority, the algorithm used information from the census tract median household income by race/ethnicity, by age, and by income, as well as the zip code median income.38,39 Patients were then ranked into quintiles based on the final composite median income value.

	Patient residence in a metropolitan (vs rural) area was also measured. This tested whether proximity to an urban area might influence the receipt of newer agents if adoption occurs earlier in urban environments.

	All analyses were conducted using commercially available software (SAS/STAT software version 9.1; SAS Institute Inc, Cary, NC). Bivariate descriptive statistics and likelihood ratio 

tests of significance were generated to compare patients initiating newer chemotherapy versus patients initiating any other chemotherapy with respect to demographic, socioeconomic, and clinical variables. Variables significantly associated with initiation of newer chemotherapy at the bivariate level (

<.05) were included in a multivariable logistic regression model to test the association between race/ethnicity or age and the odds of initiating on newer chemotherapy, while controlling for clinical and demographic factors.

	The final sample among 5068 patients with stage IV CRC receiving chemotherapy was 2466 patients. Approximately 32% of the chemotherapy users initiated their therapy using an irinotecan-containing regimen. Based on healthcare claims,the patient group using non—irinotecan-containing chemotherapy primarily received (in approximately 93% of patients) 5-fluorouracil as the cytotoxic agent.

	Results of the bivariate analysis comparing patients who initiated treatment with newer chemotherapy versus those who initiated treatment with other chemotherapy are given in 

. Race/ethnicity, sex, age, year of diagnosis, median household income, presence of comorbidities, marital status, surgery to the metastatic site, and radiation therapy were significantly associated with the receipt of newer chemotherapy agents (

 <.05). Specifically, among patients initiating treatment with newer chemotherapy, there were higher proportions of white, male, and younger patients, as well as patients diagnosed in later years (2001 and 2002), patients in higher quintiles of median household income, patients with fewer comorbidities, and married patients, compared with patients not receiving irinotecan. With respect to clinical characteristics significantly associated with the receipt of newer chemotherapy agents, fewer patients who received radiation therapy or surgery to the metastatic site (within 4 months of diagnosis) received newer chemotherapeutic agents.

	Results of the final model developed for the multivariable logistic regression analysis are given in 

. After simultaneously controlling for demographic and clinical variables significant at the bivariate level, African American race/ethnicity and older age remained significantly (

<.05) negatively associated with the receipt of newer chemotherapy agents in the logistic regression analysis. Specifically, African American patients were 35.9% less likely to initially receive newer chemotherapy than white patients (odds ratio, 0.641; 95% confidence interval, 0.453-0.907). Patients aged 71 to 75, 76 to 80, and older than 80 years were 29.2%, 47.3%, and 78.7%, respectively, less likely to initiate treatment with newer chemotherapy than patients aged 66 to 70 years (

<.05). Male patients remained significantly more likely to receive newer chemotherapy.

	This study reveals important findings with regard to the receipt of general chemotherapy and specific chemotherapeutic agent use among a Medicare sample of older patients with stage IV CRC. Approximately 49% of the final patient sample received any chemotherapy. This estimate is not directly comparable to other SEER-Medicare data because of differences in staging, disease site (colon vs rectal), and period of study, but evidence nevertheless indicates that a substantial proportion of Medicare patients with CRC do not receive chemotherapy: studies

 of SEER-Medicare older patients with stage III CRC (among whom chemotherapy benefits are widely acknowledged) indicate that the receipt of chemotherapy ranges from only 54% to 70%.

	Our study results also indicate that, among chemotherapy-receiving patients with stage IV CRC, African American patients and older patients were significantly less likely to initiate their chemotherapy with a newer agent such as irinotecan compared with white patients and younger patients. The direction of results is generally consistent with published studies

 that have evaluated racial/ethnic and age disparities among patients receiving treatment for locally advanced CRC.

	Disparities in the receipt of chemotherapy among patients with stage IV CRC have not been as widely researched as disparities among patients with earlier stages of CRC. However, McKibbin et al

 evaluated the receipt of irinotecan, oxaliplatin, or bevacizumab in patients with advanced CRC from 10 cancer centers and detected a significant association between younger age (<65 years) and increased receipt of newer chemotherapeutic agents. Furthermore, compared with patients younger than 65 years, the receipt of newer agents decreased among older patients (ie, >70 and >75 years).

 In addition, the direction of racial/ethnic and age disparities observed in the present studywas consistent with that in other observational studies

 addressing surgical management of patients with stage IV CRC.

	The existence of racial/ethnic and age differences in the receipt of newer chemotherapeutic agents among patients receiving chemotherapy indicates a persisting disparity even after selection into chemotherapy treatment. Because irinotecan was likely perceived during the study period to be a new agent with improved benefits (but with a more toxic profile), disparities in its use during that time warrant consideration. Arguably, the observed disparities may have been due to justifiable clinical or patient preference—related reasons. Conversely, these disparities may have been the result of access issues (eg, African American patients or older patients may be less able to afford a newer medication such as irinotecan) or other unmeasured factors.

	With regard to the racial/ethnic disparity observed, identifying factors driving the observed difference is challenging. There is evidence to suggest that African

	American patients are more likely to receive care from less trained primary care physicians who have fewer resources to offer patients.

 It is unknown if this finding extends to medical oncologists providing cancer care. Baldwin et al

 evaluated various patient, physician, hospital, and environmental characteristics in an attempt to identify why African American patients with stage III colon cancer were less likely to receive chemotherapy than white patients and found “no single or simple explanation.” Although African American patients and white patients were equally likely to see a medical oncologist, the authors noted that African American patients who saw a medical oncologist were less likely to receive chemotherapy. In their analyses, although oncologist characteristics such as years in practice and volume of consultations influenced the receipt of chemotherapy, disparities persisted even after accounting for these characteristics (as well as patient characteristics such as age, sex, and comorbidities).

 Almost half of the variation in the observed receipt of chemotherapy could not be accounted for. The authors suggest that other unmeasured factors such as supplemental insurance and affordability of care, as well as patient perceptions, may have a role in selection of patients into chemotherapy.

 Similar conclusions have been drawn in other analyses of the receipt of chemotherapy among patients with rectal cancer.

 It is unclear whether similar observations can be made with regard to disparities in specific types of chemotherapy selected among users, particularly patients with stage IV CRC.

	The age disparity observed may be the result of a misconception that older patients are too frail to receive chemotherapy and should not be placed on a newer and more toxic regimen.

 Evidence suggests that chemotherapy treatment recommendations in older patients can be influenced by physician characteristics such as age (with younger physicians being more likely to recommend chemotherapy) and whether he or she practiced in a teaching hospital.

 Furthermore, older patients may have difficulty than their younger counterparts in accessing more intensive healthcare services. The age disparity warrants further study, particularly in older patients who are healthy enough to tolerate aggressive therapy, among whom data demonstrate derivation of clinical benefits similar to those of younger patients.

 Like racial/ethnic disparities, age disparities are likely multifaceted and driven by patient, physician, and health system characteristics.

	Male patients were more likely to initiate treatment with newer chemotherapy than female patients. Evidence indicates that women experience more adverse effects with chemotherapy than men, a factor that may have lessened the use of the more toxic therapy in women.

 Our analysis also indicates that the receipt of newer chemotherapy was less likely to occur if the patient underwent surgery. This relationship was observed in unadjusted and adjusted analyses.

	This study has some limitations. Although the analysis involved a large cohort of SEER-Medicare patients, the exclusion criteria resulted in a considerable loss of patients, particularly patients enrolled in health maintenance organizations. Therefore, the patients in this study may not be representative of all patients with stage IV CRC. Nevertheless, given that CRC is primarily a disease of older patients,

 the information obtained with regard to drug use in the selected group of Medicare patients with stage IV disease is important to learn more about how management of the disease in this group of Medicare enrollees is evolving.

	In addition, as a result of relying on limited clinical information from SEER-Medicare data, certain variables were unavailable that may have contributed to variation in the receipt of newer chemotherapy. These include patient preferences, performance status, patient-level socioeconomic measures, and physician and hospital characteristics. Therefore, bias may exist as a result of unmeasured variables. It is difficult to state with certainty that the type of chemotherapy selected is the result of a real disparity or rather is the effect of an unobserved factor systematically distributed between racial/ethnic or age groups. Nevertheless, unobservable bias may be less pronounced between subgroups among patients who have been selected into chemotherapy. In other words, given selection into chemotherapy treatment, subgroups within chemotherapy-receiving patients are likely to be more homogeneous than broader groups of treated and untreated patients with CRC, among whom the receipt of any chemotherapy has been previously evaluated.

	Despite these limitations, this study is important in providing information about a topic (disparities in the use of novel chemotherapies) and a stage of disease (stage IV CRC) that have not been widely researched through population-based studies. Furthermore, although the study focus is on the receipt of irinotecan, information with regard to racial/ethnic and age disparities in irinotecan use is likely to be relevant to the use of newer agents with similar profiles (improved clinical efficacy but higher toxic effects, as well as costs) marketed after irinotecan.

	In conclusion, our results support the existence of racial/ethnic and age disparities in the use of irinotecan, an agent representative of a newer trend in chemotherapy treatment for patients with stage IV CRC. The results are consistent with the literature, namely, lower health services utilization in patients of African American race/ethnicity and in older patients. This utilization trend, coupled with the association of minority races/ethnicities with lower survival outcomes,

 provides further rationale for continuing to investigate the cause and extent of disparities in cancer-related health services across all stages of CRC. Additional population-based research on disparities in the use of newer agents marketed after irinotecan (eg, oxaliplatin, bevacizumab) is recommended, particularly as advances in chemotherapy regimens are taking place that lead to the questions not only of “should chemotherapy be administered” but also of “what chemotherapy should be used given the decision to treat.” Medicare Demonstration Projects & Evaluation Reports provide an excellent example of how such investigations may be studied, as do large prospective observational studies such as the Cancer Care Outcomes Research & Surveillance Consortium.

Studies have evaluated racial/ethnic and age disparities in whether patients receive chemotherapy for nonmetastatic colo-rectal cancer

Racial/Ethnic and Age Disparities in Chemotherapy Selection for Colorectal Cancer

1. Get specifics on your diagnosis and treatment.

	In order to maximize your time with your providers, bring your questions with you in writing to your appointments. Ask for copies of your test results and keep a notebook (see http://breastcancer.about.com/od/risk/p/health_records.htm) of all these results. Keep a list of questions that arise between visits so you don’t forget, and take notes of the answers. Above all, make informed decisions; learn as much as you can about your diagnosis and treatment.

	Breast cancer specialists who work at dedicated cancer centers offer specific expertise as well as access to the latest treatments that are part of clinical studies. Such centers can provide other specialty services, usually under one roof, such as physical  therapy, nutrition, and social work.

3. Get the support you need for talking about your diagnosis.

	Breaking the news to your friends and family that you’ve been diagnosed with breast cancer can be just as difficult as first hearing the news yourself from your doctor. You may feel concerned about upsetting your family and friends or worried about how they will react. Even after you have shared the news, at times you may find it difficult to communicate openly. Sometimes it’s uncomfortable to ask for help, answer questions about how you’re doing, or tell well-meaning relatives and friends that you need some time and space for yourself. If available at your hospital, request to meet with a social worker to discuss any emotional support or resource referrals you might need. A local support group for women with breast cancer may also help considerably. Ask your hospital or clinic to help you identify appropriate resources in your area.

4. Seek help in navigating financial issues, if necessary.

	Your hospital or clinic should have a social worker, patient navigator, or financial services department to help you manage financial issues and deal with private insurance companies, Medicare, and Medicaid. If you have concerns, request an  appointment.

5. Talk to your doctor about coping with menopause symptoms.

	Breast cancer patients who have undergone chemotherapy or ovary removal, or who have had to discontinue hormone replacement therapy upon diagnosis, may experience symptoms of menopause. Talk to your doctor about how to safely minimize menopausal symptoms.

	Your cancer treatment may influence your ability to taste and smell, and it may alter your digestion. Foods that you normally enjoy may not taste good during treatment while, paradoxically, foods that normally don’t appeal to you might taste better. You may prefer and tolerate more cooked versus raw vegetables, so a vegetable stew or soup may be more appealing than a salad. You may have more energy and less nausea if you eat smaller amounts of foods more frequently rather than eating three big meals per day. Try not to gain weight by overindulging and blowing your calorie budget. Help fight your cancer by eating more vegetables, fruits, whole grains, nuts, seeds, and legumes such as black beans and lentils. Choose a rainbow of colorful whole foods (like deep greens of spinach, deep blues of blueberries, white for onions, and so on) to ensure that you get a variety of anticancer nutrients. Alcohol is usually not preferred or recommended during treatment, but if you do drink, limit your intake to no more than three drinks per week. Recent studies have shown an association between alcohol and increased risk of breast cancer.

	Lymphedema is a side effect of breast cancer treatment that involves swelling of the soft tissues of the arm, hand, or chest wall. It isn’t life threatening, but it needs to be treated to avoid getting worse. The swelling may be accompanied by numbness,  discomfort, and infection. There’s no reliable way to assess your risk for lymphedema, but by taking proper precautions you can greatly reduce your chances of developing the condition. Ask your doctor about scheduling physical therapy if you notice symptoms, or consider seeing a physical therapist even before symptoms begin in order to minimize their chance of developing in the first place.

	Gentle exercise during treatment, such as regular walks, can help with both the mental and physical effects of treatment. After treatment is completed, increasing your exercise gradually will help improve your fatigue and rebuild muscle tone. Getting your circulation going may also help with chemobrain, the mental fogginess noticed by some patients during and after chemotherapy, and it can certainly improve your mood and your outlook on life. Try yoga, tai chi, swimming, or water aerobics. Be physically active for at least 30 minutes every day. If you are having difficulty exercising or aren’t sure what to do, request a referral to a physical therapist from your medical provider.

	Keeping your bones healthy throughout your life is important; however, if you’re a woman who’s been diagnosed with breast cancer, bone health is especially important. Research shows that some breast cancer treatments can lead to bone loss. Plus, women are about twice as likely as men to develop osteoporosis after age 50. Talk to your healthcare team about specific recommendations for keeping bones healthy, taking calcium and vitamin D, and appropriate weight-bearing exercises to help keep bones strong.

	Some people are able to work throughout their cancer treatment. Yet for some, reducing one’s work capacity or taking a break altogether may be necessary. If you take time off and then return to work shortly after your treatment ends, you may find that it helps you maintain your identity and even boosts your self-esteem, not to mention your income. You may want to talk with your employer about options such as flextime, job sharing, or working from home. Options like these may help your mind and body ease back into the demands of your job. Try to be patient and take care of yourself as you go back to your “normal” life.

10 helpful tips to remember during treatment for patients struggling with breast cancer

10 Tips for Breast Cancer Patients During Treatment

back the deadline for issuing a final ruling on the Biologic Licensing Application that Bristol-Myers Squibb (BMS) submitted for its promising advanced melanoma drug ipilimumab. The agency had agreed to give the novel drug a priority review, and a decision had been expected by December 25, 2010. The agency subsequently asked BMS for additional information and further analysis of the data. BMS promptly complied with this request, but the FDA said the new information resulted in a “major amendment” to the BLA. It now expects to announce its decision on March 26, 2011.

become the third tyrosine kinase inhibitor approved by the FDA as a first-line treatment for patients with newly diagnosed Philadelphia chromosome—positive (Ph ) chronic myeloid leukemia (CML) in the chronic phase. It joins Gleevec (imatinib), the first targeted agent approved for this indication, and its offspring Tasigna (nilotinib). Unlike Gleevec and Tasigna, which primarily inhibit the BCR-ABL protein associated with Ph CML, platelet-derived growth factor receptor, and KIT, Sprycel inhibits BCR-ABL and Src. The FDA granted accelerated approval to Sprycel in 2006 as a second-line therapy in patients who were resistant to or intolerant of imatinib. None of these approved agents is effective in patients with CML who have the T135I mutation.

 the FDA launched an investigation into whether the gonadotropin-releasing hormone (GnRH) agonists used to treat advanced prostate cancer contributed to an increased patient risk of diabetes and cardiovascular disease. The agency reviewed several studies that had suggested a possible relationship between GnRHs and these conditions. In October, the FDA announced that although the risk was small, it was statistically significant. Now, the agency wants GnRH manufacturers to add new safety information to their labels that warn physicians and patients of the risks. Products subject to the ruling include leuprolide acetate (Eligard, Lupron, Lupron Depot, Viadur); goserelin acetate (Zoladex); triptorelin pamoate (Trelstar); and histrelin acetate (Vantas).

 that it intends to reclassify digital mammography systems approved in the United States as Class II devices. Currently, the systems are designated Class III devices. It is anticipated that this change will make it easy for manufacturers of these screening and diagnostic devices to get approval. Class II devices are associated with medium risk to patients and are considered safer than Class III devices. The FDA said it had several discussions with the public and medical experts and was reassured that evidence shows the technology is safe for screening and diagnosing breast cancer.

that it has granted orphan drug status to ensituximab (NPC-1C), an investigational drug being developed by Neogenix Oncology as a therapy for pancreatic cancer. Ensituximab is a chimeric monoclonal antibody. Neogenix is investigating the novel agent in a phase I clinical trial for patients with previously treated advanced pancreatic cancer and colorectal cancer. The company has received two federal grants to help fund its research into ensituximab under the Patient Affordability Care Act.  Orphan Drug Status is designed to make it easier for companies to develop new drugs for rare conditions affecting <200,000 Americans.

 Afinitor (everolimus), marketed by Novartis Pharmaceuticals, has been given accelerated approval by the FDA to treat nonresectable subependymal giant cell astrocytoma (SEGA). These benign tumors are associated with tuberous sclerosis, a rare genetic disorder that occurs more frequently in children and adolescents. The oral drug was approved to treat SEGAs after a single-arm study showed that 32% of patients with SEGA experienced a ≥50% reduction in tumor volume after 6 months of therapy and none developed a new SEGA after a median of 2 years of therapy with Afinitor. Complete findings appear in the November 3 issue of the 

Further Winter 2010 FDA Updates

 Drugs  Advisory Committee recommended that the FDA approve AstraZeneca’s novel drug Zactima (vandetanib) for patients with medullary thyroid cancer, which is a rare form of the disease. Noting concerns about the drug’s potential to cause cerebrovascular events, including stroke, and prolonged QT intervals, the panel recommended restricting use of the drug to patients with symptomatic disease. Panel chair Wyndham Wilson, MD, chief of Lymphoma Therapeutics with the National Cancer Institute, said despite concerns about Zactima’s toxicity profile, “I think we all agree it’s a very effective new agent and should be made available.

 the benefit of using 5-alpha reductase inhibitors, such as Avodart (dutasteride) and Proscar (finasteride), to reduce the risk of prostate cancer. These drugs are presently approved to treat benign prostatic hypertrophy. One trial found 4 years of chemoprevention with GlaxoSmithKline’s Avodart reduced prostate cancer risk by 23%. In advance of an upcoming advisory panel meeting, the FDA has posted briefing documents on its Website noting that dutasteride raised the incidence of high-risk prostate cancer. Merck, which manufactures Proscar, is asking to change its label to reflect study findings that show it reduced the rate of low-risk prostate cancer but is not seeking a new indication for the drug.

Winter 2010 | Special Issues

Miles for Hope: Cancer Survivor Works to Raise Awareness and Funding for Brain Tumor Research

The Aggressive Peripheral T-Cell Lymphomas

Resection and Reconstruction of a Solitary Sternal Metastasis After Mastectomy for Breast Cancer: A Case Report and Review of the Literature

Racial/Ethnic and Age Disparities in Chemotherapy Selection for Colorectal Cancer

10 Tips for Breast Cancer Patients During Treatment

Further Winter 2010 FDA Updates

Winter 2010 FDA Updates

Oncology Research Moves Us Closer to Our Goal

A Look Inside and a Look Ahead

Adjuvant Therapy for Non-Small Cell Lung Cancer: Impact of Recent Clinical Trials on Community Practice