SWOG Shares Trio of Studies in San Antonio

SWOG is an international cancer clinical trials network funded by the National Cancer Institute (NCI), part of the National Institutes of Health (NIH). In results they will share in posters presentations in San Antonio, all three SWOG researchers mined existing SWOG trial data to ask fresh, important questions about breast cancer.

“This work is creative and relevant, and shows breast cancers in all their complexity,” said Julie Gralow, MD, the SWOG executive officer overseeing breast cancer research and an internationally acclaimed cancer researcher and physician. “Breast cancers and breast cancer patients present in multiple ways. In these three studies, SWOG researchers share results that better define subsets of patients and tumors with respect to treatment response, toxicities, and cancer recurrence. These are strong examples of our work.”

• Priyanka Sharma, MD, of University of Kansas Cancer Center and vice chair of the SWOG breast cancer committee, will present results of the first study to examine the long-term outcomes of patients with different molecular subtypes of triple negative breast cancer (TNBC). Using samples from S9313, a SWOG breast cancer trial that banked hundreds of tumor tissue specimens, Sharma and her team conducted microarray profiling on these samples to generate specific TNBC subtypes – Basal Like 1 (BL1), Basal Like 2 (BL2), Mesenchymal (M), Mesenchymal Stem-like (MSL) and Luminal Androgen Receptor (LAR). Tissue samples were also tested for immunomodulatory status, or signs of immune system activation. Sharma and her team then looked at patient outcomes after S9313 patients were treated with adjuvant doxorubicin and cyclophosphamide (AC) chemotherapy to see what the prognosis was for each subtype. They found that patients with BL1 subtype (about 24 percent of the total) had the best outcomes; They remained free of disease the longest. On the other end of the spectrum, patients with the MSL and LAR subtypes (which made up about 21 percent of the total) were more likely to have their cancer return.

“This shows that TNBC isn’t just one disease,” Sharma said. “We’re now beginning to understand the molecular diversity of this type of breast cancer – and we need to test different treatments on these different subtypes in clinical trials.”

• Darya Kizub, MD, of The Everett Clinic in Seattle, will present the answer to a question that has intrigued some breast cancer clinicians and researchers: Would statin drugs reduce the risk of cancer recurrence among post-menopausal women with early stage breast cancer? Results from laboratory and observational studies have suggested that these cholesterol-fighting drugs might have cancer-fighting benefits as well – particularly in combination with bisphosphonates, drugs that prevent the loss of bone density and are often prescribed to post-menopausal women after breast cancer treatment. Kizub mined data from S0307, a SWOG trial testing the effectiveness of bisphosphonates after breast cancer surgery, and analyzed outcomes for the women enrolled on S0307 who took statins (684 patients) and those that didn’t (1,848 patients). Kizub and her team found no evidence that statins either reduced the risk of developing a second breast cancer tumor, or reduced the risk of breast cancer spreading to the liver, bone, or brain. In addition, despite promising pre-clinical data, there was no evidence that statins and bisphosphonates worked together to reduce cancer recurrence.

“Our results make it clear that there is no synergistic, cancer-fighting effect when statins and bisphosphonates are taken together,” Kizub said. “It will take a clinical trial to settle the question of whether statins have an impact on cancer recurrence.”

• Lynn Henry, MD, PhD, of Huntsman Cancer Institute at the University of Utah and co-chair of SWOG's symptom control and quality of life committee, will present findings that show that obese patients get more benefit from duloxetine to treat symptoms of joint pain that plagues tens of thousands of postmenopausal women each year who are treated with aromatase inhibitors (AIs) for their breast cancer. Two years ago at the San Antonio Breast Cancer Symposium, Henry gave a special plenary presentation on S1202, her SWOG trial that showed that duloxetine, a drug typically used to treat depression and anxiety, can alleviate the pain caused by AIs, a common breast cancer medication used to treat postmenopausal women. This year, at the Annual Meeting of the American Society of Clinical Oncology (ASCO), her SWOG colleague, Sherry Shen, MD, presented findings that showed omega-3 fatty acid supplements can significantly reduce AI joint pain – but only for obese women, or those with a body mass index over 30. Henry wanted to look back at her own S1202 data to see if obesity was a predictor of response to duloxetine. It was, according to her analysis of 289 patients who enrolled in S1202 – 54 percent of whom were obese. Obese patients enrolled in the trial received more benefit from duloxetine compared to non-obese patients.

“We need more studies to understand the biological basis for these findings, but the clinical implications are clear,” Henry said. “For AI symptom management, physicians should consider duloxetine for pain for their breast cancer patients, particularly women who are obese. The better women manage their pain, the more likely they are to continue their AI treatment, and get the benefits of better health and better quality of life that comes with that treatment.”

Sharma’s research was funded by the National Institutes of Health through NCI grants CA180888 and CA180819, and in part by Amgen, an ASCO Advanced Clinical Cancer Research Award, the Eileen Stein Jacoby Fund, the Breast Cancer Research Foundation, and the University of Kansas Cancer Center’s Biospecimen Repository Core Facility through grant P30 CA168524.

Kizub’s research was funded by the National Institutes of Health through NCI grants CA180888, CA180819, CA180820, CA180821, CA180868, CA180863, the Breast Cancer Research Foundation, Susan G. Komen, Berlex Laboratories, Inc., Novartis, and Genentech, a member of the Roche Group.

Henry’s research was funded by the National Institutes of Health through NCI grant CA189974, a Damon Runyon-Lilly Clinical Investigator Award #C1-53-10, Lilly USA, and The Hope Foundation for Cancer Research.