San Antonio Breast Cancer Symposium 2013 Highlights:
A Focus on Neoadjuvant Triple-Negative Breast Cancer
Two interesting neoadjuvant clinical trials for patients with triple-negative breast cancer were presented:
(1) CALBG/Alliance 40603: This study randomized triple-negative breast cancer patients to receive carboplatin, a DNA-damaging chemotherapy, plus or minus bevacizumab, a drug that slows the growth of new blood vessels, in addition to standard dose-dense doxorubicin, cyclophosphamide, and paclitaxel (the AC-T regimen) and showed that the patients on both the carboplatin plus standard chemotherapy and carboplatin, bevacizumab plus standard chemotherapy had a greater chance of having little to no residual disease in the breast and axilla (or armpit) at the time of lumpectomy or mastectomy. <More details>
This is a very important finding as previous studies have shown that women with localized triple-negative breast cancer, who have no or minimal residual breast cancer in the breast and the axilla at the time of surgery, have a prognosis that is similar to women with estrogen receptor-positive and progesterone receptor-positive breast cancer.
Unfortunately, as we add more agents to the AC-T backbone, the toxicity profile worsens, too, and this was also shown, with the patients in the combined carboplatin and bevacizumab arm having the highest toxicity profile, including low blood counts and hypertension (a side effect of bevacizumab). The study is still in its early stages and as such we do not have information on overall survival and progression-free survival in the experimental arms, however the addition of DNA-damaging chemotherapy, such as platinum agents in triple-negative breast cancer is an area of active research and as such we are sure to hear more about regimens such as this one in the near future.
(2) I SPY 2 trial-- first efficacy results: This study is part of a national multi-drug Phase II clinical trial that aims to identify biomarkers that can predict response to specific therapies for women with locally advanced breast cancer. The study is open at UCSF, UCSD and USC in California. Similar to the CALGB 40603 trial described above, this study showed that adding carboplatin and a molecularly targeted drug named Veliparib, which also leads to DNA damage, in addition to standard neoadjuvant chemotherapy, improves the likelihood of achieving a complete pathologic response at the time of surgery (i.e. no residual cancer in the breast or the axillary lymph nodes) for women with triple-negative breast cancer, and, in previous trials, this has been linked to improved overall outcomes.
As mentioned, veliparib is a targeted DNA-damaging agent and is in a class of agents named "PARP" inhibitors. In early phase clinical trials these types of agents have also been shown to be effective for women with BRCA1- or BRCA2-associated breast and ovarian cancers, and currently several phase III clinical trials are underway to investigate this further.
These two interesting pre-operative therapy studies show that women with triple-negative breast cancer have a higher likelihood of responding to agents that damage DNA due to the underlying gene mutations that are linked to this type of breast cancer. In the coming years, we will hear about the phase III clinical trial results and the impact on survival that this type of therapy will offer. Furthermore, it is exciting that targeted agents are being evaluated for triple-negative disease, which by definition has been thought of as the breast cancer type that "lacks a target."