Oncology research continues to occur at a rapid pace, creating a number of novel systemic therapies and strategies that have recently entered clinical practice in the field of breast cancer. At the Braman Family Breast Cancer Institute at the University of Miami’s Sylvester Comprehensive Cancer Center, physicians and scientists are collaborating to bring these treatments to patients with clinical trials.

In the area of adjuvant treatment, continued small incremental gains have contributed to the steady decrease in breast cancer mortality. In women with early-stage breast cancer, extending the duration of adjuvant tamoxifen therapy from 5 to 10 years reduces the risk of recurrence and breast cancer mortality, according to updated results of the aTTom trial. Compared with 5 years of tamoxifen, 10 years of tamoxifen was associated with a 15% reduction in the risk of recurrence and a 25% reduction in the risk of breast cancer mortality starting at year 10.

For HER2+ breast cancer, the success of trastuzumab in the adjuvant and metastatic setting has opened the door for the development of other HER2 targeted therapies which are now approved including lapatinib, pertuzumab, and ado-trastuzumab. Pertuzumab is a HER2 dimerization inhibitor, and is approved in the first line metastatic setting in combination with trastuzumab and docetaxel. It was recently approved in the neoadjuvant setting in combination with trastuzumab and chemotherapy.

In the adjuvant setting, the combination of trastuzumab and pertuzumab for one year vs the standard of trastuzumab alone, is the subject of an ongoing trial. Ado-trastuzumab is an antibody-drug conjugate that was approved by the FDA February 2013 for the treatment of HER2-positive metastatic breast cancer previously treated with a taxane and trastuzumab. Ado-trastuzumab is now being evaluated in a number of clinical settings, including as adjuvant therapy and for those patients who have less than a pathologic complete response at the time of surgery after receiving neoadjuvant chemotherapy.

Another HER2 targeted therapy, Neratinib, is currently not approved. This is an oral, multi-targeted, irreversible tyrosine kinase inhibitor and is currently under investigation in the metastatic setting. Thus, patients with HER2 positive breast cancer have an expanding menu of options for treatment.

For hormone receptor positive, HER2 neu negative patients, definition of pathways that mediate eventual resistance to hormone therapy in the metastatic setting is an area of active investigation. The mTOR inhibitor, Afinitor, when combined with exemestane, markedly prolonged progression free survival in patients who had progression on a non-steroidal aromatase inhibitor. An exciting class of drugs called CDK inhibitors continue to demonstrate encouraging results when combined with hormonal therapy. The addition of one such agent, PD-0332991, to letrozole increased median time to disease progression to 26.1 months compared with 7.5 months for letrozole alone. This oral, relatively non-toxic therapy will represent a considerable improvement in options for hormone receptor positive patients.

Finally, for triple negative breast cancer (TNBC), it is becoming clear that this subtype is quite heterogenous, not only on the molecular level, but also on pathologic and clinical levels. Nevertheless, studies of neoadjuvant chemotherapy suggest that women with TNBC who have a pathological complete response (pCR) to treatment achieve excellent outcomes. A recent study incorporating the use of carboplatin in the neoadjuvant setting demonstrated an increased in the pCR rate from 46% to 60%. Whether this approach will also be supported in the adjuvant setting, remains to be seen.

These important findings represent just a few of the latest advances in the treatment of breast cancer; advances that will ultimately lead to a more personalized approach to cancer treatment.