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Oncology-Advances-January-2016

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Dana-Farber/Brigham and Women's Cancer Center | 7 Refer a Patient to Dana-Farber/Brigham and Women's Cancer Center For more information or consultation, please call 1-877-332-4294 to speak with one of our experienced referral coordinators. We now offer next business day access for first appointments at our main campus in Boston. Mehra Golshan, MD Dr. Abdul Mohsen and Sultana Al-Tuwaijri Distinguished Chair in Surgical Oncology, Brigham and Women's Hospital; Medical Director, International Oncology Programs, Dana-Farber/Brigham and Women's Cancer Center Researchers Investigate Ductal Cell Carcinoma In-Situ, Propose Less Aggressive Strategies for Low-risk Lesions Breast cancer specialists in the Susan F. Smith Center for Women's Cancers at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) are pioneering efforts to identify subsets of patients with ductal cell carcinoma in-situ (DCIS) who might appropriately avoid aggressive treatment. DCIS has traditionally been treated with lumpectomy (with or with- out radiation) or mastectomy, despite the fact that fewer than 50 percent of cases become invasive tumors. "What we have seen with DCIS is that more cases are identi- fied with better imaging, but there appear to be subgroups of women with lesions that are unlikely to spread or become invasive," said Mehra Golshan, MD, the Dr. Abdul Mohsen and Sultana Al Tuwaijri Distinguished Chair in Surgical Oncol- ogy at Brigham and Women's Hospital and Medical Director, International Oncology Programs, DF/BWCC, "So then the question becomes, how much treatment do these patients re- ally need?" No Survival Benefit from Surgery in Low-risk DCIS Dr. Golshan and Yasuaki Sagara, MD, a former research fellow at BWH, recently led a groundbreaking retrospective study demonstrating that surgery had no impact on survival among women with low-grade (e.g., low mitotic rate) DCIS (JAMA Surg. 2015 Aug 1; 150(8):739-745). Their team of international collaborators reviewed 57,222 DCIS cases tracked by the National Cancer Institute's Surveillance, Epidemiology and End-Results (SEER) database. According to the results, surgi- cally treated women had a weighted 10-year breast cancer- specific survival rate of 98.5 percent compared to 93.4 percent in the non-surgical group. However, among the subgroup of women with low-grade DCIS, the surgical and non-surgical survival rates were nearly identical: 98.8 percent and 98.6 per- cent respectively. "This was the first large study with a significant number of pa- tients who never had surgery for DCIS and the results suggest that surgery does not improve overall survival outcomes for the low-risk population," Dr. Golshan said. Dr. Sagara added, "Our findings suggest we might consider new management strategies for low-grade DCIS, such as ac- tive surveillance or anti-estrogen therapy, while continuing to recommend surgery for intermediate- and high-grade le- sions." Two randomized trials now ongoing in Europe, Dr. Sagara said, are investigating whether active surveillance is feasible and safe following a DCIS diagnosis. Shrinking DCIS Lesions with Letrozole Dr. Golshan is currently the principle site investigator of a sin- gle-arm phase 2 clinical trial (CALBG 40903) examining whether anti-estrogenic therapy interferes with the growth of DCIS lesions before surgery. Investigators hypothesize that es- trogen-receptor positive (ER+) lesions will shrink or disappear with neoadjuvant treatment, reducing the need for surgical in- tervention. The study has a target accrual of 96 post- menopausal women with ER+ or progesterone-receptor positive (PR+) DCIS who receive letrazole orally once daily for six months followed by breast magnetic resonance imaging (MRI) and then lumpectomy or mastectomy. The primary study objective is to determine whether letrozole reduces DCIS tumor volume. Secondary objectives are to as- sess if MRI findings correlate with treatment-induced changes in histopathology, and whether letrozole treatment leads to re- ductions in Ki67, a marker for breast cancer cell proliferation. According to Dr. Golshan, positive findings could set the stage for targeted DCIS management strategies that for some pa- tients could result in incorporating endocrine therapy and ac- tive surveillance rather than undergoing surgery and radiation. DCIS Outcomes in Patients Treated with Radiation and Surgery Drs. Golshan and Sagara are also collaborating on a study ex- amining factors associated with survival outcomes for patients with DCIS who undergo lumpectomy followed by radiation therapy. "We're searching through SEER data for simple parameters such as age, use or radiation therapy, the grade and size of DCIS lesions, that help us identify who might not benefit from radiation treatment," Dr. Golshan said. "A prognostic score that combines known predictive factors of local DCIS recur- rence could help with decisions on whether to omit radiother- apy after lumpectomy. We hope our study will facilitate these types of tailored treatment strategies."

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