Joyce A. O'Shaughnessy, MD, Texas Oncology-Baylor Charles A. Sammons Cancer Center, discusses what recent research has shown regarding phosphoprotein assays in treatment decision-making for patients with breast cancer.

It has been interesting to use phosphoprotein assays in patients with triple-negative breast cancer (TNBC) who are refractory to treatment, O’Shaughnessy says. In matching genomics with phosphoprotein assays in TNBC with 

 mutations, researchers have observed a phosphoprotein pattern in activation of the MAPK pathway through EGFR. This could potentially lead to new treatment for this subgroup of patients, O’Shaughnessy explains.

In recent cases of patients with refractory TNBC and high levels of phosphorylated EGFR who were treated with investigational agents, O’Shaughnessy says their EGFR became obsolete and their disease turned chemotherapy-sensitive.

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Dr. O'Shaughnessy on Phosphoprotein Assays for Treatment Decision-Making for Breast Cancer

Joyce A. O’Shaughnessy, MD, the Co-Director of Breast Cancer Research at the Baylor Charles A. Sammons Cancer Center; Texas Oncology, PA/US Oncology, Dallas, Texas, discusses the evolving area of breast cancer subtype-specific cytotoxic agents.

It is difficult to understand different types of triple-negative breast cancer (TNBC) today, O’Shaughnessy says, as there are no laboratory tests in this space. There are data coming out that show certain chemotherapy agents may be more effective for TNBC than they are for ER-positive disease.

O’Shaughnessy says that there are some subtype-specific differences with cytotoxic agents but we are still in the early days of research.

Joyce A. O'Shaughnessy, MD, discusses the evolving area of breast cancer subtype-specific cytotoxic agents.

Dr. O'Shaughnessy on Breast Cancer Subtype-Specific Cytotoxic Agents

Joyce A. O’Shaughnessy, MD, the Co-Director of Breast Cancer Research at the Baylor Charles A. Sammons Cancer Center; Texas Oncology, PA/US Oncology, Dallas, Texas, reviews findings from Study 301, which compared eribulin mesylate (Halaven) to capecitabine for patients with locally advanced or metastatic breast cancer.

In the trial, 1102 women received eribulin or capecitabine as a first-, second-, or third-line treatment. However, O'Shaughnessy notes, the majority of the patients had received a prior anthracycline, making the trial essentially a second-line comparison.

Overall, the results were equivocal for the primary endpoint of overall survival (OS). Despite this, O'Shaughnessy believes the trial was positive for eribulin, since it demonstrated equivalence to one of the best agents in this setting. Additionally, she adds, a subset analysis revealed that treatment with eribulin prolonged OS by nearly 5 months more than capecitabine in patients with triple negative breast cancer.

An observational trend favoring eribulin was observed for OS; however, no difference was noticed for progression-free survival (PFS). This is similar to observations made in the EMBRACE trial, which compared eribulin to physician's choice in patients with heavily pretreated metastatic breast cancer. These data suggest that eribulin does not affect OS through PFS, instead, O'Shaughnessy believes, eribulin may sensitize the tumor to other cytotoxic agents.

In general, O'Shaughnessy notes, Study 301 was an interesting trial, which provides support for moving eribulin forward in the sequence to the second-line of treatment in metastatic breast cancer.

Joyce A. O'Shaughnessy, MD, from the Baylor Charles A. Sammons Cancer Center, reviews findings from Study 301, which compared eribulin mesylate to capecitabine for patients with locally advanced or metastatic breast cancer.

Dr. O'Shaughnessy on Eribulin in Metastatic Breast Cancer

Joyce A. O’Shaughnessy, MD, the Co-Director of Breast Cancer Research at the Baylor Charles A. Sammons Cancer Center; Texas Oncology, PA/US Oncology, Dallas, Texas, describes potentially practice changing findings from the BOLERO-3 trial.

In the phase III BOLERO-3 trial, weekly trastuzumab and vinorelbine where administered with or without everolimus in trastuzumab-resistant, advanced HER2-positive breast cancer. According to a press release, O'Shaughnesy states, the triplet of everolimus, trastuzumab, and vinorelbine improved progression-free survival in patients with metastatic breast cancer.

This trial suggests a viable new option for patients with HER2-positive disease, O’Shaughnessy believes. Moreover, everolimus is already approved, which allows for immediate use in this space.

Looking closer at the patient population in the trial, O'Shaughnessy notes interest in exploring the differences observed between subgroups of patients with HER2-positive and ER-positive disease. This desire is enhanced by positive data from the BOLERO-2 trial, which examined everolimus plus exemestane in patients with ER-positive, HER2-negative advanced breast cancer.

O'Shaughnessy anticipates that further data supporting the everolimus treatment strategy will likely be presented in the BOLERO-2 biomarker analysis. Furthermore, she notes special interest in the occurrence of PIK3CA mutations, which predict the effectiveness of everolimus.

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Joyce A. O'Shaughnessy, MD, the Co-Director of Breast Cancer Research at the Baylor Charles A. Sammons Cancer Center, describes potentially practice changing findings from the BOLERO-3 trial.

Dr. O'Shaughnessy on Everolimus in Breast Cancer

Joyce A. O'Shaughnessy, MD, Co-Director, Breast Cancer Research, Baylor Charles A. Sammons Cancer Center, Texas Oncology, US Oncology in Dallas, TX, describes the upcoming School of Breast Oncology conference as a very practical hands on course.

It contains a great deal of value for any member of the multidisciplinary oncology team that is working through the decision making process. It touches on day-to-day state-of-the-art care and contains lengthy case discussions. The meeting is very hands on for medical, surgical, physicians’ assistant, nurse practitioners, and radiation oncologists.

Dr. Joyce A. O'Shaughnessy from the Baylor Sammons Cancer Center Describes the School of Breast Oncology

Dr. O'Shaughnessy Describes the School of Breast Oncology

Joyce A. O'Shaughnessy, MD, Breast Cancer Research, Baylor Sammons Cancer Center in Dallas, TX, discusses the future of triple-negative breast cancer (TNBC) treatments.

O'Shaughnessy believes that TNBC is the biggest challenge currently facing breast cancer treatment. There is currently a large amount of testable hypotheses that may result in a major break-through. These hypotheses will further be strengthened by the results of the The Cancer Genome Atlas (TCGA) project for breast cancer.

The TCGA results should be submitted by the end of this year. A full sequence analysis of breast cancer will not only illuminate TNBC but also will shed light on potential subtypes of TNBC.

Dr. Joyce A. O'Shaughnessy from Baylor Sammons Cancer Center on the Future of Triple Negative Breast Cancer Treatment

Dr. O'Shaughnessy on the Future of TNBC Treatment

Joyce A. O'Shaughnessy, MD, Co-Director, Breast Cancer Research, Baylor Charles A. Sammons Cancer Center, Texas Oncology, US Oncology in Dallas, TX, describes that the future of breast cancer treatment will include improved monitoring practices, more knowledge of disease biology, and new agents.

The number of biopsies completed needs to increase in metastatic disease overall and biopsies need to be repeated at multiple intervals for patients with longer histories. In addition to biopsies real-time monitoring will become more important in the next 5 years using circulating tumor cell changes as an indicator.

O'Shaughnessy believes the outlook for HER2-positive breast cancer is very bright as more agents are made available and new subtypes are discovered potentially through the evaluations of phosphoproteins.

In estrogen receptor (ER) positive breast cancer an increased understanding of the biology of indolent cancer will lead to a better interpretation of treatment options. Exploring the molecular pathogenesis and necrosis may lead to the realization that indolent ER-positive breast cancer requires prolonged endocrine therapy.

Treatments for aggressive ER-positive breast cancer require an increased familiarity of the disease’s molecular and pathway abnormalities. Various trials are currently underway for aggressive ER-positive cancer; including the BOLERO-2 trial examining everolimus (Afinitor) and the entinostat (SNDX-275) phase II trial that was presented at the 

10th Congress on the Future of Breast Cancer

Dr. Joyce A. O'Shaughnessy from Baylor Sammons Cancer Center on the Future of Breast Cancer Treatment

Dr. O'Shaughnessy on the Future of Breast Cancer

Joyce A. O'Shaughnessy, MD, Breast Cancer Research, Baylor Sammons Cancer Center in Dallas, TX, begins by mentioning that the HER2 marker is already a focused part of breast cancer. She believes that some biomarker selection will become necessary and that it is no longer feasible to approach the adjuvant setting with a mixed population of patients with triple-negative breast cancer and indolent ER-positive breast cancer.

O'Shaughnessy believes it is not feasible to find a selection marker for everything, but she believes some selection needs to take place. There is a great deal of systems biology that comes into play when dealing with breast cancer. Because of its complex nature it may not be possible to know every operative pathway and microenvironment, at this time, but a basic understanding of the biology is needed

Future selection of patients may also be based not only on a positive outcome but also a negative. If you know a patient will not respond positively because they posses a certain marker you may exclude them from studies. Using biomarkers in this way can be just as useful as a positive outcome.

There is currently a great deal of effort being focused on discovering very narrow subsets of patients, and this will produce some success, but in the long run O'Shaughnessy believes broader based biological subsets will be more successful.

Dr. Joyce A. O'Shaughnessy from Baylor Sammons Cancer Center on the Future of Breast Cancer Biomarkers

Dr. O'Shaughnessy on Breast Cancer Biomarkers

Joyce A. O'Shaughnessy, MD, Breast Cancer Research, Baylor Sammons Cancer Center in Dallas, TX, describes that iniparib's mechanism of action (MOA) is still under intensive study and has been under examination since the drug was first discovered.

Despite its recent negative triple negative breast cancer (TNBC) trial results O'Shaughnessy believes iniparib will become interesting once again. She describes that in a physiological concentration you do no inhibit PARP but in higher concentrations inhibition does occur. She believes that once the MOA is fully understood more options will be available.

Other trials are currently underway examining iniparib; options are becoming clear, such as its single agent use in BRCA2 mutated pancreatic cancer. It is still being investigated in TNBC, which O'Shaughnessy believes is still too broad of a category. A subset of patients in the TNBC trial demonstrated a benefit to the drug; trials still need to be conducting to pinpoint this subset of patients.

Dr. Joyce O'Shaughnessy from Baylor Sammons Cancer Center on Negative TNBC Iniparib Trial Results

Dr. O'Shaughnessy on Negative TNBC Iniparib Results

Program Director Joyce A. O'Shaughnessy, MD, Breast Cancer Research, Baylor Sammons Cancer Center in Dallas, TX, explains that Avastin (bevacizumab) remains her standard of care for aggressive metastatic breast cancer that requires the use of two agents for optimal control.

She explains that the using two chemotherapy agents may not be sustainable for longer periods of time; whereas paclitaxel in combination with Avastin offers better options for doublet therapy. She believe that Avastin also fulfills is biggest unmet medical need in triple negative breast cancer which is often refractory to chemotherapy.

Dr. Joyce A. O'Shaughnessy from Baylor Sammons Cancer Center on Avastin as Her Standard of Care

Dr. O'Shaughnessy on Avastin as Her Standard of Care

Joyce A. O'Shaughnessy, MD, Breast Cancer Research, Baylor Sammons Cancer Center in Dallas, TX, describes that all she truly needs is access to Avastin (bevacizumab) as a treatment option for breast cancer. She believes that with its many other approvals, both in the US and in the Europe, it will continue to be accessible with a large amount of information available on its use. Having tools, such as Avastin, readily available that are non-cross resistant with chemotherapy is necessary for patients with very few options left.

Dr. Joyce A. O'Shaughnessy from Baylor Sammons Cancer Center on Continued Access to Avastin

Joyce A. O'Shaughnessy, MD

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