Major Advance: PARP Inhibitor Pill Extends Life For Women With High Risk Breast Cancer & BRCA Mutations

A major new study has found that for women with early stage breast cancer classified as (HER2)–negative, who also have one of the mutations from the BRCA gene, a relatively new class of drugs called PARP Inhibitors significantly extends life after initial treatment.

Published Jun 3, 2021

Alison Maxwell

PARP Inhibitors For Breast Cancer

  • Major new study provides new hope for women with early stage breast cancer classified as HER2 negative, who also have genetic mutations known as BRCA.
  • A class of drugs called PARP Inhibitors (in this case the drug is Olaparib) extended life for women who had received a first course of surgery and or radiation and chemotherapy.
  • Leading breast cancer experts say this new evidence is likely to change how some women are treated.

There’s encouraging news for some early stage breast cancer patients.

A major new study published in The New England Journal of Medicine has found that a relatively new class of drugs called PARP Inhibitors significantly extends life for women with early stage breast cancer classified as HER2 negative. Importantly, these women also have a genetic mutation known as BRCA.

One year of treatment with the PARP inhibitor called olaparib (brand name: Lynparza) following surgery and/or chemotherapy significantly reduced the risk of recurrence and prevented the cancer from spreading in HER2 negative, high risk patients with the BRCA1 or BRCA2 genetic variant.

The trial’s numbers are impressive. The three year survival rate without a recurrence of what’s called invasive breast cancer was 85.9% for patients treated with olaparib, compared to 77.1% in the placebo group.  The trial included 1,836 patients from 420 centers across 23 countries. The research will be presented at the 2021 American Society of Clinical Oncology (ASCO) annual meeting, which is the largest conference of cancer doctors.

RELATED: PARP Inhibitors Provide New Promise For Certain Metastatic Breast Cancers

“This is definitely an exciting trial with exciting results,”says SurvivorNet Medical Advisor Dr. Elizabeth Comen, who treats breast cancer patients at Memorial Sloan Kettering Cancer Center. “We’ve been studying PARP inhibitors for nearly 10 years and its exact role in improving outcomes for patients, particularly early stage breast cancer patients, has yet to be definitively seen. The reason for the excitement for this trial is that it essentially showed that people who are at high risk for recurrence in early breast cancer, so not metastatic, with BRCA1 or BRCA2 mutations had significantly longer survival free of invasive or distant disease than placebo.”

Dr. Sylvia Adams, director of the breast cancer center at NYU Langone’s Perlmutter Cancer Center and professor of medicine at NYU Grossman School of Medicine, tells SurvivorNet the results of the study are so promising that this treatment plan could become a new standard of care.

“While long-term follow-up is needed for overall survival and to monitor for certain late toxicities, data to date show a significantly longer survival free of breast cancer for patients who received olaparib and I expect this will become a new standard of care for BRCA-related breast cancers,” Dr. Adams says. “To put this into context, this treatment would be added after surgery (+radiation if indicated) as well as completion of chemotherapy and only for patients at high risk of recurrence.”

Olaparib is given orally and is already approved to treat metastatic breast cancer patients and advanced ovarian cancer patients with the BRCA gene variant. Side effects are generally less invasive than those accompanying chemotherapy and can include nausea, vomiting, headache and diarrhea.

Breast cancer is the most common cancer in American women, except for skin cancers. The average risk of a woman in the United States developing breast cancer sometime in her life is about 13%. About 5-10% of breast cancers involve the BRCA1 or BRCA2 genetic variant.

What is a PARP Inhibitor?

PARP inhibitors are a relatively new form of targeted therapy that can stop cancer cells from spreading by preventing them from repairing their damaged DNA, causing them to die. The FDA approved them for the treatment of BRCA-mutation-related metastatic breast cancer in 2018. Those kinds of cancers are more likely to be triple negative breast cancer, which can be more aggressive. Data has shown that women who received PARP inhibitors did better overall than patients who received chemotherapy.

“This broadens our arsenal for the treatment of triple negative breast cancer beyond conventional chemotherapy,” says Dr. Heather McArthur, medical director of breast oncology at Cedars-Sinai Medical Center.

Patients can be born with BRCA mutations or acquire them over time.

“BRCA is responsible for DNA repair. So for people who have a mutation in the BRCA region, they’re not able to successfully repair DNA damage, which is necessary for cell survival,” explains Dr. McArthur. “So PARP inhibitors also interfere with DNA repair. So in people who already have a DNA repair defect (such as BRCA), to further impair those redundant repair mechanisms  has been a successful strategy in women with BRCA mutation carrier-related breast cancers.”

Dr. Heather McArthur talks PARP inhibitors for metastatic breast cancer

Why Genetic Testing is So Important

Typically doctors recommend genetic testing only for women who have a family history of rare cancers, or family members with breast or ovarian cancer and other cancers associated with the Lynch Syndrome (a genetic condition that puts you at high risk for certain cancers), or if there’s a family history of common cancers diagnosed at a young age.

But Dr. Comen notes that the results of this study “bring up the point about whether we should increase testing across the board for early breast cancer patients who may have a mutation that we’re missing.” Dr. Adams agrees: “(The study) does have implications to broaden criteria for genetic testing of patients newly diagnosed with breast cancer.”

Dr. Comen explains: “Normally we think about evaluating for mutations only in people who have very strong family histories, but not all patients with BRCA1 or BRCA2 mutations have a known strong family history, or have been checked for these mutations, and it really begs the question of patients with early stage breast cancer to ask their doctor if they’ve not yet been tested if this is something I should be tested for.”

Another important reminder is to think about your entire family’s history when discussing genetic concerns. “When they talk about their genetic history with their doctor it’s not just their mother’s side it’s their father’s side which is a common misconception,” Dr. Comen says.

If you need assistance with discovering your genetic risk, ask about your cancer center’s hereditary cancer program and/or find a genetic counselor through the National Society of Genetic Counselors (NSGC ) to discuss what kind of genetic testing is right for you.

Should I Get Genetic Testing to Assess My Risk for Breast Cancer?

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Alison Maxwell is the executive editor at SurvivorNet. Read More