More Triple Negative News from San Antonio

Neoadjuvant Therapy is More Effective for Very Young Breast Cancer Patients

A study done by the German Breast Group reviewed the data from eight trials in which patients with breast cancer received neoadjuvant chemotherapy prior to their surgery. Their goal was to compare the rates of complete pathologic responses-meaning that there was no evidence of disease at the time of surgery-and then compare the overall disease free survival, local recurrence free survival and overall survival by groups.

Approximately a third of the patients of the very young patients (35 and under) had TNBC, with the percentage decreasing in the older age groups. The study found that the youngest patients, those in the 35 and under group had the highest rate of pathologic complete responses. In that group, the TNBC patients had the highest response rate of all, 35%.

The group concluded that very young women were more likely to achieve a complete response after neoadjuvant therapy and that this response improved their survival. They also concluded that breast cancer in the very young is biologically different than in older patients.

This is a strong argument for having neoadjuvant chemotherapy, an approach that is becoming the standard of care for young patients and those with TNBC.

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HDAC Inhibitors Enhance Treatment with PARPs and Cisplatin

HDACs or histone deacyetylase inhibitors work by damaging DNA and depleting the levels of special proteins in the cells that repair this damage. A study done by a group at the University of Kansas provides evidence that combining these HDAC inhibitors with PARP inhibitors and cisplatin creates a synergistic effect that causes TNBC cells to die. The trial supports beginning new trials that combine these agents.

Kapil N. Bhalla, MD, who presented the study said, "Complex biology requires complex combinations of therapy."

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Profiling TNBC after Neoadjuvant Chemotherapy Identifies Targetable Molecular Changes

This study relates directly to the emerging information about the biological and genetic character of TNBC, and has direct clinical implications. In this study reported by Justin Balko, MD, of Vanderbilt-Ingram Cancer Center, researchers did molecular profiling for TNBC patients who had residual disease after they finished their neoadjuvant therapy. Having residual disease after finishing pre-surgery chemotherapy is generally associated with a poorer prognosis, but as Dr. Balko stated, "Up to now, we have not known how to treat these patients. We don't have any targeted therapies."

This work represents a step towards changing that picture. The group analyzed 114 TNBC tumors and found a wide range of mutations. Approximately 90% of patients had at least one mutation that could potentially be targeted with drugs. They also identified a mutation, JAK2, not previously known to exist in TNBC, in 11% of patients. While patients with this mutation appear to have a worse prognosis, it is a potentially targetable with new therapies.

One important finding is that many patients have more than one mutation which means that in order for treatment to be effective, it will probably be necessary to use more than one agent. The key, according to Balko, is to distinguish the true driver mutations, the ones that are essential to cancer growth, from those that do contribute to cancer growth and spread.

This study provides strong support for doing genetic sequencing on TNBC tumors, and initiating new clinical trials using molecular targets as adjuvant therapy for women with residual disease following surgery.

Christine Wilson for TNBC Foundation

Angie