Tailor-Made for a Lifelong Pursuit of Precision in Cancer Care

From a young age, Joseph A. Sparano, MD, FACP, had an interest in science and medicine. However, it was his personal experience with cancer that truly set him on the path to becoming an oncologist.

Growing up in a tight-knit immigrant household in the Bronx, New York, Sparano witnessed his maternal grandmother’s battle with locally advanced breast cancer firsthand. Her experience with the disease, which eventually claimed her life, left a lasting impression on Sparano and instilled in him a profound desire to improve outcomes for patients with cancer in underserved communities—a mission that has defined his research and career in oncology.

Sparano, who was named a 2024 Giant of Cancer Care inductee in breast cancer, is renowned for his groundbreaking contributions to both breast cancer and HIV-associated cancer research, as well as his commitment to addressing racial disparities in cancer care. He has led several pivotal National Cancer Institute (NCI)–backed trials that have shaped the treatment paradigm and clinical practice guidelines in breast cancer, including the phase 3 TAILORx (NCT00310180) and E1199 (NCT00004125) trials. He is also involved in several international efforts to improve outcomes for patients with AIDS- related malignancies.

“Dr Sparano is a true giant of our field, who I have had the great fortune to know and learn from for close to 30 years,” said Sparano’s long-time collaborator and colleague Balazs Halmos, MD, who has witnessed his outstanding work and leadership as a dedicated clinician in their time working together at Montefiore Einstein Comprehensive Cancer Center in the Bronx. “[He is] most definitely a role model to me and so many others. He is humble, consistent, focused, accomplished, and—first and foremost— always placing patients first.” Halmos is the associate director of clinical science at Montefiore Einstein.

Sparano's Path to a Career in Breast Oncology

With a clear sense of purpose, Sparano was initially set to attend Columbia University for his undergraduate pre-med studies, until he learned that he was accepted by the 6-year BS-MD Sophie Davis School of Biomedical Education Program at the City College of New York, now the CUNY School of Medicine. The program’s focus was on preparing students with diverse backgrounds for careers in medicine with a focus on community service, which provided him with a strong foundation that later became central to his work in caring for Black and Hispanic residents of the Bronx, where he spent his childhood and most of his career.

“[I’ve] always had an interest in medicine and science as far back as I can remember, but the focus on oncology crystallized during my medical school education,” Sparano said. “By the time I finally entered oncology training, I had previously considered other specializations in cardiology or infectious diseases.”

After finishing his undergraduate studies in 1980, Sparano went on to earn his medical degree from New York Medical College in 1982. His residency in internal medicine at St Vincent’s Hospital in Manhattan coincided with the height of the AIDS epidemic—a time when the medical community was grappling with the complexities of a new and deadly disease. This experience further solidified his interest in oncology, as he witnessed the increasing incidence of cancers among patients with HIV.

“In the beginning of the HIV epidemic, we were seeing young men and women die of opportunistic infection,” Sparano said. “Then, as more effective antivirals became available and these patients were surviving, we were seeing more HIV-associ- ated cancers, especially aggressive lymphomas and rapidly progressive Kaposi sarcoma. That influenced my decision to eventually choose medical oncology for my training.”

Once his residency had been completed, Sparano completed a fellowship in medical oncology at Montefiore Medical Center and the NCI-designated Albert Einstein Cancer Center in the Bronx, New York. It was here that he began to hone his research skills, explore a variety of research avenues, and continue to foster his passion for treating patients with breast cancer and HIV- associated cancers.

“At the time, there was a tremendous amount of enthusiasm about the use of immunotherapeutic approaches to treat cancer using high-dose IL-2,” Sparano said. “That was a focus of my career for the first 3 to 5 years. There was also a lot of enthusiasm and interest in high-dose chemotherapy with stem cell transplantation, so I was [also] involved in that program. It wasn’t until 1995 that I started to transition more to fully focus on breast cancer and HIV- associated cancers.”

Following the completion of his fellowship, Sparano became involved in the Eastern Cooperative Oncology Group (ECOG), which later merged with the American College of Radiology Imaging Network (ACRIN) to become ECOG-ACRIN. “I attended my first ECOG meeting in the 1990s as a junior faculty member. Because of my interest in breast cancer, I became involved in the Breast Cancer Committee and served as the liaison to the Biological Response Modifier Committee, as it was called at the time.”

After contributing to several phase 2 trials through the program that evaluated various chemotherapy combinations, Sparano was appointed vice chair of the Breast Cancer Committee in 2005 by the previous chair, George W. Sledge Jr, MD, of Stanford Medicine, and a 2018 Giant of Cancer Care inductee in breast cancer. “I served as his cochair for [several] years. When he stepped down to become president of [the American Society of Clinical Oncology (ASCO)], I assumed the breast chair role,” Sparano said.

Ongoing Contributions to Breast Cancer Research: Beginning With TAILORX

It was during his time as vice chair of the ECOG Breast Committee that one of Sparano’s most notable contributions to breast cancer research, the TAILORx trial, was conceptualized.2 This landmark study, conducted from 2006 to 2010, enrolled more than 10,000 women and was the first NCI precision medicine trial to utilize the 21-gene expression Oncotype DX assay to assess the risk of disease recurrence in patients with estrogen receptor (ER)–positive, HER2-negative breast cancer. Before TAILORx, the standard of care (SOC) for patients with early-stage breast cancer often involved chemotherapy, regardless of individual risk factors and despite the treatment’s significant adverse effects (AEs).

“Prior research had shown that [this] test provided potentially useful prognostic information, and possibly predictive information for chemotherapy benefit in women with ER-positive, HER2-negative, node-negative breast cancer, which accounts for about one-half of all breast cancers in the US. We also knew only about 5% derived chemotherapy benefit, but didn’t know enough about who actually benefited most from treatment,” Sparano said.

TAILORx aimed to address this issue by determining whether patients with a low or intermediate Oncotype DX recurrence score (RS) of up to 25 could safely avoid chemotherapy without compromising their prognosis. The trial’s results, initially published in The New England Journal of Medicine in 2015, established that patients with a very low RS of 0 to 10 had excellent outcomes with endocrine therapy alone. A subsequent publication in The New England Journal of Medicine in 2018 that was presented at the 2018 ASCO Plenary Session showed that chemotherapy provided no benefit for the majority of women with a RS of 11 to 25, including women older than 50 years or postmenopausal at diagnosis, as well as most younger women who had a RS of 0 to 15.

Sparano’s work on TAILORx has had a profound impact on patient care, sparing thousands of women from the potentially harmful AEs of chemotherapy, and impacting clinical practice guidelines worldwide. In addition, he also contributed validation of the ductal carcinoma in situ (DCIS) score, a genomic test that assesses the risk of recurrence in patients with this noninvasive form of breast cancer. The test helps inform which patients with DCIS have the highest recurrence risk, and therefore most likely to benefit from radiation in addition to surgery.

A Drive to Decrease Disparities in Breast Cancer Care

A significant focus of Sparano’s research has been understanding the factors that contribute to racial and ethnic disparities in cancer outcomes, particu- larly those of Black women with breast cancer. “It had been long known that Black women with breast cancer had worse outcomes due to [several] factors, including a more advanced stage of presentation, a lack of access to screening and care, a higher risk of comorbidities preventing women from getting adequate treatment, and higher rates of obesity and...triple-negative breast cancer associated with a higher recurrence rate and mortality,” Sparano said.

In his analysis of data from the phase 3 E1199 trial, Sparano and his team found that even among women receiving the SOC, Black patients with ER-positive, HER2-negative breast cancer experienced worse outcomes compared with White patients, and had a 2-fold higher risk of developing taxane-inducted neuropathy compared with White women.3

This work served as the impetus for the development of the first NCI-sponsored trial designed specially to include only Black women with early-stage breast cancer who required adjuvant taxane chemotherapy, the phase 2 ECOG-ACRIN EAZ171 trial (NCT04001829). The prospective validation trial aimed to identify genetic variants that were associated with higher taxane- induced peripheral neuropathy rates in Black women.

Although genetic predictors could not be confirmed, it was shown that Black women had higher neuropathy rates with weekly paclitaxel vs docetaxel every 3 weeks, leading to the development of novel strategies for risk reduction.4

A Dual Research Focus on HIV-Associated Cancers

Although breast cancer research has been a major focus of Sparano’s career, his expertise extends to another critical area of oncology: HIV-associated cancers. His work in this field has led to advancements in the specialized treatment of HIV- positive patients with non-Hodgkin lymphoma and anal cancer. As chair and principal investigator of the NCI-Funded AIDS Malignancy Consortium since 2020, he has played an instrumental role in developing new treatment protocols and expanding knowledge of the unique challenges experienced by this patient population.

“In the mid-1990s, we were seeing a lot of patients with HIV who presented with very aggressive, advanced lymphomas,” Sparano said. “We performed a series of studies through my own institution [and] the AIDS Malignancy Consortium, testing infusional chemotherapy approaches and immunotherapy approaches.”

Through this research, Sparano and colleagues developed the regimen of rituximab (Rituxan) plus etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride for the management of HIV-associated lymphomas, which has since become a SOC.5 Additionally, Sparano led an international team in performing a meta-analysis of HIV-lymphoma trials, which resulted in a new prognostic score for this disease: the AIDS-related lymphoma International Prognostic Index.6

“My passion for this research is driven by the fact that it helps inform the care of patients [who] I see every day in [the] clinic,” Sparano said.

Beyond the Bench: Sparano's Legacy of Mentorship and Compassionate Care

Sparano’s current research endeavors continue to push the boundaries of oncology. Leveraging biospecimens from the TAILORx trial, Sparano and colleagues aim to investigate the molecular foundation of breast cancer recurrence, particularly in patients with low-risk scores. He is also exploring the role of clonal hematopoiesis and genetic determinants in breast cancer outcomes,with the goal of developing more personalized treatment strategies.

Outside the lab, Sparano continues to see patients in his new role as chief of the Division of Hematology and Medical Oncology, and deputy director of the NCI-funded Tisch Cancer Institute at the Icahn School of Medicine in New York. He also remains deeply committed to mentorship, which reflects his own valuable experiences as a mentee.

His mentorship has shaped the careers of many young oncologists, including Jesus D. Anampa, MD, MS, an associate professor of oncology at the Albert Einstein College of Medicine and director of clinical and translational breast cancer research in the Department of Breast Medical Oncology. Anampa recalls the pivotal moment when Sparano invited him to join the breast cancer team. “I still remember, it was a Friday night after a busy day on the oncology floors when I received the phone call from Dr Sparano inviting me to join the breast cancer team. That event changed my entire career. I remember that I was [beginning to feel] disappointed because I had applied to a few grants, which were not funded. Dr Sparano told me...‘If you keep throwing darts, eventually you’ll hit the bullseye.’ It was such an amazing lesson about persistence.”

Despite his demanding career, Sparano still finds time for his hobbies, including cycling, boating, and diving into a good book—particularly historical biographies. Sparano and his wife of 42 years, Lori, have been married since his medical internship. He has 2 daughters, Alyssa and Jennifer, and 2 grandchildren with whom he enjoys spending quality time.

Ultimately, Sparano’s unwavering dedication to his patients’ wellbeing, groundbreaking research across tumor types, and commitment to addressing disparities in cancer care all add to his contributions in the field of oncology.

As Halmos aptly puts it: “Whether shining at the ASCO plenary session presenting practice-changing work or working diligently in the clinic, Joe consistently has been a stellar role model for me and our entire field. Really, he is just tailor-made—or one could say TAILORx-made—for this award.”

References

1. Joseph A. Sparano, MD. Mount Sinai Health System. Accessed August 15, 2024. https://profiles.mountsinai.org/joseph-a-sparano
2. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379(2):111-121. doi:10.1056/NEJMoa1804710
3. Kim G, Pastoriza JM, Qin J, et al. Racial disparity in distant recurrence-free survival in patients with localized breast cancer: a pooled analysis of National Surgical Adjuvant Breast and Bowel Project trials. Cancer. 2022;128(14):2728-2735. doi:10.1002/cncr.34241
4. Schneider BP, Zhao, F, Ballinger TJ, et al. ECOG-ACRIN EAZ171: prospec- tive validation trial of germline predictors of taxane-induced peripheral neuropathy in Black women with early-stage breast cancer. J Clin Oncol. 2024;42(24):2899-2907. doi:10.1200/JCO.24.00526
5. Sparano JA, Lee JY, Kaplan LD, et al. Rituximab plus concurrent infu- sional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood. 2010;115(15):3008-3016. doi:10.1182/ blood-2009-08-231613
6. Barta SK, Xue X, Wang D, et al. A new prognostic score for AIDS-related lymphomas in the rituximab-era. Haematologica. 2014;99(11):1731-1737. doi:10.3324/haematol.2014.111112