2012: Advancing our Knowledge of Breast Cancer Treatment
Guest blog from Kelly Graham-Seyed, Susan G. Komen for the Cure Scientific Grants Manager
In 2012, researchers and clinicians have made key advances in breast cancer therapy. Many clinical trials focused on combinations of therapies that have been administered as standalone treatments in the past. The immune response has also played a role in new therapy development, and new treatment regimens have been introduced to enhance therapies currently implemented in the clinic.
Timing is everything In a study from MIT and Harvard, the efficacy of combination therapies for triple-negative breast cancers was studied in animal models. The research team found that therapies were more effective in shrinking tumors and preventing regrowth when two drugs were given sequentially, with a delay or “rest period” between the first and second treatment.
Using Tumor Genetics to Inform Therapy Komen Scholar Matthew Ellis found that ER+ breast tumors had distinct mutations that correlated with response to aromatase inhibitor treatment. Tumors that harbored MAP3K1 mutations generally had a low grade (more normal) cell type, and slower growth; these tumors were more likely to respond to aromatase inhibitor therapy prior to surgery. Tumors that harbored tp53 mutations generally had a higher grade (more abnormal) cell type and a faster cell doubling rate; these tumors were less likely to respond to aromatase inhibitor treatment. These gene mutations may help doctors determine who should receive pre-surgical aromatase inhibitor therapy in the future.
Immune Cells Give Trastuzumab a Leg Up A study out of Stanford University showed that trastuzumab, a drug that targets the HER2 receptor, is enhanced when immune cells with CD137 molecules present on their surface are activated. This finding will help develop more effective drug combinations for treating HER2+ breast tumors in the future.
Introduction of Novel HER2 Therapy Regimens in the Clinic
T-DM1: A New Therapy in the Clinic One of the most talked about studies this year was the EMILIA trial, which provided the groundwork to establish trastuzumab emtansine (T-DM1) as a new therapy for metastatic HER2+ breast cancer. Komen Scholar Kimberly Blackwell unveiled the results at the American Society of Clinical Oncology meeting this past summer. The trial showed that T-DM1 provides significant and clinically meaningful improvement to metastatic breast cancer patients, providing a 3-month increase in progression-free survival and an 18% increase in overall survival after 2 years versus the current standard of care (capecitabine + lapatinib).
Optimization of Herceptin Timing The phase III HERA trial run by the Breast International Group showed that a two-year regimen of trastuzumab (marketed as Herceptin) does not have any advantages over a one-year regimen. The PHARE trial shortened the duration of treatment one step further and compared 12-month and 6-month regimens of trastuzumab. Although the results weren’t statistically significant, the data trended in favor of a 12-month regimen. If confirmed, these studies may suggest that HER2+ breast cancer patients may benefit from a shorter treatment time with trastuzumab.
New Therapy Combinations Results from the CLEOPATRA trial, headed by Komen Scholar Jose Baselga, demonstrated that adding pertuzumab to the standard regimen of trastuzumab and docetaxel improves progression-free survival by about 6 months versus trastuzumab and docetaxel alone. Roche conducted a Phase III trial using a combination Herceptin-Perjeta therapy, and reports that the risk of death from HER2+ breast cancer was reduced by 34% in women treated with the combination treatment compared to Herceptin alone. If further testing follows suit, these novel therapy combinations may provide HER2+ breast cancer patients with options for new and effective treatments.
Timing of Tamoxifen Treatment This year, results from the Adjuvant Tamoxifen – Longer Against Shorter (ATLAS) trial have been updated: researchers are starting to see a trend that premenopausal ER+ breast cancer patients who take tamoxifen for 10 years instead of the NCI-recommended 5 years may reduce their risk of breast cancer relapse.
New Therapy Combinations for ER+ Breast Cancer The BOLERO-2 trial headed by Komen Scholar Jose Baselga showed that adding everolimus to exemestane treatment in metastatic hormone receptor positive breast cancer patients resulted in a median 6.5 month increase in progression free survival compared to exemestane treatment alone. The Phase II TAMRAD trial provided clinicians with a new, potentially more effective treatment by combining tamoxifen and everolimus as a treatment for metastatic hormone receptor positive breast cancer. After a 6-month follow-up, 61% of patients did not experience tumor progression compared to 42% on tamoxifen alone. These trial results suggest that new treatment options for metastatic ER+ breast cancer survivors may be on the horizon.
New Therapies for Estrogen Receptor Negative Breast Cancers
Chemotherapy After Surgery is Effective
The CALOR trial, run by the International Breast Cancer Study Group studied the effects of chemotherapy after surgery in triple negative breast cancer patients. The results showed a 67% disease-free survival rate for women who received chemotherapy versus a 35% disease-free survival rate for the non-chemo breast cancer patients after 5 years of follow-up. Overall survival after 5 years differed by 10%, with 79% of chemotherapy-treated patients and 69% of non-chemotherapy-treated patients experiencing overall survival. These results suggest that post-surgery chemotherapy may be an option that triple negative breast cancer patients and their doctors should consider.
Vaccinations Enhance Patient’s Immune Response to Triple Negative Breast Cancer
A clinical trial out of MD Anderson Cancer Center has shown that administering vaccines to turn on immune response cells in triple negative and HER2-low breast cancer patients may help a patient’s own immune system to fight the tumor. The results from this study are preliminary, but promising; the patients’ own immune responses to their triple negative breast cancers persist after initial vaccination.
Improving Treatment for Metastatic Triple Negative Breast Cancer
A Phase II clinical trial that tested everolimus and carboplatin combination therapy was studied in metastatic triple negative breast cancer patients. Early results show that 38% of patients had a clinical benefit, defined as a partial or complete regression of the detectible cancer, or a stabilization of the cancer for at least 6 months. While additional studies are needed, these results are promising for the metastatic triple negative breast cancer community.
Looking Ahead to 2013 and Beyond
We at Komen and the breast cancer community are forever indebted to the people who make the clinical trials possible: the thoughtful and dedicated clinicians and researchers and the brave patients who participate in clinical trials. These trials have laid the groundwork for future advances for breast cancer therapies and improvements for standard of care.
About the author
Nancy G. Brinker promised her dying sister, Susan G. Komen, she would do everything in her power to end breast cancer forever. In 1982, that promise became Susan G. Komen for the Cure and launched the global breast cancer movement. Today, Komen for the Cure is the world’s largest grassroots network of breast cancer survivors and activists fighting to save lives, empower people, ensure quality care for all and energize science to find the cures. Thanks to events like the Komen Race for the Cure®, we have invested more than $1.9 billion to fulfill our promise, becoming the largest source of nonprofit funds dedicated to the fight against breast cancer in the world.