By Karuna Jaggar, Executive Director
Triple negative breast cancers are defined by the lack of targeted therapy available for women with this type of breast cancer. Where women with hormone positive breast cancers can benefit from hormone therapies, like tamoxifen and aromatase inhibitors, and HER2+ breast cancers benefit from targeted therapies like Herceptin and Bevacizumab, treatment for triple negative breast cancers are limited to the slash/burn/poison of surgery/radiation/chemotherapy. Where once women with HER2+ breast cancers were considered to have the worst outcomes since the development of targeted HER2 therapies, the terrible distinction of worst outcomes of breast cancer subtypes now goes to triple negative disease. Here are some updates on triple negative disease from this year’s San Antonio Breast Cancer Symposium.
Two trials reported on Wednesday afternoon looked at carboplatin to treat triple negative breast cancer. Prior data has not established a role for this highly toxic treatment in early stage triple negative breast cancer.
The strongest data was presented by the CALGB/Alliance in the GeparSixto trial (S2-04) which reported improved disease free survival after 35 months for patients with triple negative breast cancer treated with carboplatin before surgery (neoadjuvant): 53.2% on the carboplatin arm compared to 36.9% on the control arm. There was no benefit for patients with HER2+ breast cancer. The authors conclude that GeparSixto supports the use of carboplatin as part of neoadjuvant treatment for all patients with triple negative breast cancer.
However, the next presentation from CALGB/Alliance (S2-05) showed different results. Data was presented from this randomized phase II trial of 454 patients in a 4-arm trial with paclitaxel alone or combined with either bevacizumab (Avastin) or carboplatin, or all three treatments combined. The data did not confirm benefit of carboplatin or bevacizumab to patient outcomes, but nor did the presenter insist that the data refuted efficacy.
Individual doctors and patients will reach different conclusions in looking at this data. At this stage, the data is provocative but it remains an individual decision if carboplatin is appropriate for all triple negative breast cancers, given the high toxicity and inconclusive data. Each woman and her doctor must decide if the possible benefit is worth the trade-offs, in particular long-term toxicity.
Dr. Cliff Hudis, from Memorial Sloan-Kettering, noted the limitations of defining triple negative breast cancer by what it is not, saying “If you don’t live in California and you don’t live in New York, that doesn’t make you a Texan!”
Researchers had previously found that there was a category of triple negative breast cancers whose gene expression looked like estrogen positive breast cancer, but they lacked both messenger RNA for the estrogen receptor and the estrogen receptor itself. These researchers found that, in fact, the androgen receptor was present on these cancers and they look like prostate cancer. More patients with triple negative breast cancer have these androgen sensitive tumors than previously thought.
Several effective advances in prostate cancer have been directed at the androgen receptor, which is a critical component in the treatment of prostate cancer. Although androgen positive (AR+) breast cancer is a different entity than androgen driven prostate cancers, researchers have done early experiments with some of these treatments for women with androgen positive triple negative breast cancer. In effect, this means that now there may be a hormone therapy for a group of patients for whom we previously lacked a targeted therapy, indeed whose disease is defined (triple negative) by lack of targeted therapy.
The mantra of breast cancer has become “one size does not fit all” and there are “subtypes within the subtypes”. As researchers investigate the range of characteristics within the broad group of triple negative breast cancers, new subtypes may emerge, with targeted therapies for some. But this trend to disaggregate cancer subtypes also brings with it challenges and risks of essentially creating “orphan diseases” within breast cancer, and proof of safety and efficacy are more challenging with smaller and smaller trials. As with so many things, the more we learn, the more we learn what we don’t know.