Positive News For Triple Negative Breast Cancer

By Kathleen Hoffman, PhD, MSPH

Almost 150,000 patients and caregivers have interest in, have joined communities, have searched and posted about breast cancer and advanced breast cancer on Inspire. Almost 22,000 posts have been written about breast cancer research.

There has been intense interest in finding medications that can penetrate the 10-20% of breast cancers that don’t respond to the medications that target three hormone and protein receptors on the tumor cell’s surface. When a breast tumor cell lacks the receptors for estrogen, progesterone, or HER-1 or -2 on the surface, it’s classified as “triple negative breast cancer” (TNBC).2

Members eagerly share updates as this member did:

I have been treated…for metastasized TNBC…There are several studies addressing combination therapies for many solid tumors and I would love to hear from you about your experience.

who also quoted from the journal, Drugs, that a drug called sacituzumab govitecan (Trodelvy™) had been approved to treat solid tumors including triple negative breast cancer.

Another member said:

I was diagnosed with Tri-Neg BC in November of ____ and was scared to death. Poorer prognosis is all I could hear. But almost three years later I am cancer free (NED) and now I know that chemo works especially well for Tri-Negs and after five years the risk of recurrence goes way down – even below the positive receptors status risks. So while it may sounds scary…it is very doable.

TNBC is an aggressive form of breast cancer–the cells are more undifferentiated (do not look like normal cells) and tend to be basal-like cells– that don’t respond to targeted treatments. It is known to metastasize more readily and to recur after treatment.

Since surgery I had NED on any scans. This February there was a small something suspicious, they looked into it more, planned a biopsy then skin nodules developed. They biopsied THOSE and they came back positive. Its TNBC again.

However, there are finally treatments showing effectiveness against TNBC in two different targeted drug classes: an immunotherapy and two PARP inhibitors.3

On July 21, 2021, the FDA approved pembrolizumab, an immune checkpoint inhibitor (immunotherapy), as a drug that can be used to treat early-stage TNBC. Pembrolizumab is approved for use with chemotherapy as a treatment before surgery to shrink the tumor (neoadjuvant treatment) and also as a single agent to continue after surgery. Before this, pembrolizumab was only available to patients with TNBC whose tumors expressed PD-L1 and whose tumors could not be surgically resected.4,5

The approval was based on the results of a clinical trial, KEYNOTE 522, which found that the rate of pathologic complete response (pCR) (no sign of cancer after treatment) was 63% compared with 56% for patients who received chemotherapy alone. At 3-years follow-up the rate of event-free survival was still higher than without pembrolizumab.4,6

Results from a Phase III trial of olaparib, a PARP inhibitor approved for treatment of ovarian cancer, also show that PARP inhibitors are effective in treating breast cancers that have BRCA1 or BRCA2 mutations. This includes TNBCs that have the BRCA mutations.

The clinical trial, OlympiA, is showing that olaparib increases disease free survival after surgery, an outcome that was described as “practice-changing” in an ASCO expert roundtable. One of the panel members, Dr. Jennifer Litton, professor of medicine and vice president of clinical research at MD Anderson’s Comprehensive Cancer Center, said she considers the use of PARP inhibitors for these patients a new “standard of care,” and recommends broadening the use of genetic testing for all patients to determine if they have applicable mutations.7,8

In the same webinar, the panel discussed results of another study that was also presented at ASCO’s annual meeting this year. The NEOTALA Phase II study showed promise that another PARP inhibitor, talazoparib, can be effective for the pre-surgical treatment of triple-negative breast cancer. Preoperative chemotherapy is the standard-of-care for most early-stage TNBC. Talazoparib is an oral drug, (one pill per day). It is hoped that the trial will continue to show positive results that will eventually enable this group of patients to have an alternative to chemotherapy.8,9

This is encouraging news. Finally, there are targeted treatments showing effectiveness against TNBC in two different drug classes: The immunotherapy, pembrolizumab, is approved. The PARP inhibitors in clinical trials are promising agents for women with breast cancer who have the BRCA1 or BRCA2 mutation, and there may even be simple oral alternatives to chemotherapy in the future. Bench research along with clinical trials are making a difference.

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1 Syed Y. Y. (2020). Sacituzumab Govitecan: First Approval. Drugs, 80(10), 1019–1025. https://doi.org/10.1007/s40265-020-01337-5
3 https://www.mayo.edu/research/forefront/team-ids-genes-boost-risk-triple-negative-breast-cancer?_ga=2.132121930.53800970.1629210074-711500827.1586369351
5 https://www.cancer.gov/publications/dictionaries/cancer-terms/def/neoadjuvant-therapy
6 https://www.cancer.gov/search/results?swKeyword=pathologic+complete+response