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BCRF Investigators Develop Test to Guide Treatment Decisions Before and After Neoadjuvant Therapy

By BCRF | May 31, 2017

Counting dividing tumor cells after starting treatment may predict which breast cancer patients with estrogen receptor positive disease are at high risk of recurrence.

Women diagnosed with larger tumors, typically stage II- III, may receive chemotherapy prior to surgery – called neoadjuvant therapy–to reduce the size of the tumor, which can allow for less extensive and breast conserving surgery.  

For postmenopausal women with larger estrogen receptor (ER)-positive breast cancers, anti-estrogen therapy, such as an aromatase inhibitor (AI), has been shown to be very effective in reducing the mastectomy rate without the toxicity of chemotherapy. However, some women will still need the additional chemotherapy to achieve the best long-term results.  Being able to identify who still needs chemotherapy early will improve the success of neoadjuvant therapy, while sparing women who don’t.

In previous work supported in part by BCRF Investigator Dr. Matthew Ellis and colleagues in the Alliance for Clinical Trials in Oncology  (ALLIANCE) developed a test that measures the presence of tumor and tumor cell proliferation (active cell division) to determine whether a patient should be switched to a more aggressive chemotherapy.

The test measures proliferation twice after starting antiestrogen therapy. The first is measured after two to four weeks to identify poor responders who need additional treatments. The second uses a surgical specimen to generate a score called PEPI (preoperative endocrine proliferation index). If validated, the PEPI score may be used to identify patients in whom the antiestrogen alone is sufficient treatment.

Dr. Ellis and colleagues recently reported results from a substudy of the ALLIANCE Z1031 clinical trial showing that women who had a PEPI score of zero after AI neoadjuvant therapy has a very low risk of recurrence within 5 years (the median follow up time for the substudy).

“These findings provide further evidence that antiestrogen-based neoadjuvant therapy an effective alternative to chemotherapy in terms of improving breast conservation,” Dr. Ellis said.

The investigators also noted that those women with PEPI higher than zero also tended to be resistant to added chemotherapy, highlighting the need to better understand the biology driving resistance to anti-estrogen therapy and find alternate treatments.

“This approach also provides information on antiestrogen response that can be used to individually adapt the treatment approach so that patients get a treatment plan that is more closely guided by the biological characteristics of her tumor,”Dr. Ellis added.

Dr. Ellis and colleagues are continuing to study and refine the use of the PEPI score in the ongoing ALTERNATE phase III clinical trial with support from BCRF.  The study was published in the Journal of the Clinical Oncology.