Study: Breast cancer treatment combination and dose improves survival in people with inherited BRCA1 and BRCA2 mutations

RELEVANCE

Most relevant for: People newly diagnosed with early-stage breast cancer who have BRCA1 or BRCA2 mutations.

It may also be relevant for:

• people with breast cancer
• people with a genetic mutation linked to cancer risk
• people newly diagnosed with cancer

Relevance: Medium-High

Strength of Science: High

Research Timeline: Post Approval

More rating details

What is this study about?

This study focused on the treatment given before surgery (neoadjuvant therapy) for people with a BRCA1 or BRCA2 mutation who have early-stage breast cancers. The researchers tested whether a PARP inhibitor called Lynparza (olaparib) and chemotherapy can be safely given together if the dose schedule is optimized.

These two treatments are not typically given together, due to the risk of serious bone marrow side effects, such as lowered counts of red blood cells (anemia), platelets and white blood cells. However, the researchers timed the treatments so that the combination was not only safe but also led to better survival outcomes.

Why is this study important?

This study provides an improved treatment for people with a BRCA1 or BRCA2 mutation who have early-stage breast cancer.

Inherited BRCA1 or BRCA2 mutations greatly increase the risk of developing breast or ovarian cancer and are also linked to prostate and pancreatic cancers. PARP inhibitors are a type of targeted therapy developed to treat cancers among people with a BRCA1 or BRCA2 mutation. PARP inhibitors have typically been given alone. The PARP inhibitor Lynparza (olaparib) is an especially effective treatment for early-stage BRCA1- or BRCA2-related breast cancers that have a high risk for recurrence. Chemotherapy is also used to treat these breast cancers.

This study showed that:

• Changing a dose schedule makes it possible to give two drugs together that previously could not be safely used at the same time.
• The combined treatment used in this trial may be a more effective presurgery therapy for early-stage breast cancer among people with a BRCA1 or BRCA2 mutation than the current standard of care (chemotherapy alone).
• The presence or absence of cancer cells after presurgery treatment may not predict the survival of people with BRCA-related breast cancers.

Study findings

The PARTNER trial included 106 people with early-stage breast cancer who had an inherited BRCA1 (73%) or BRCA2 (27%) mutation. The PARP inhibitor tested was Lynparza; the chemotherapy tested was carboplatin. The study set out to identify the most effective dose schedule against cancer with the least amount of bone marrow toxicity, a known side effect of these treatments that is more common when they are combined.

Researchers took three steps to find the best combined therapy option:

1. Assessed three different dose schedules to determine the safest schedules for combining Lynparza with chemotherapy.

2. Compared the two safest schedules to each other. The researchers determined that the least toxicity occurred when there was a 48-hour wait time between Lynparza and chemotherapy.

3. Compared the combined therapy (with the 48-hour wait time) to chemotherapy alone to see which was the most beneficial for patients.

Key findings

Findings from the study highlight the following points regarding the safety, effectiveness and side effects of combining Lynparza with chemotherapy before surgery:

• A safer way to combine treatments
  • The PARP inhibitor Lynparza and chemotherapy can be safely given together before surgery (neoadjuvant therapy) when there is a 48-hour gap between chemotherapy and Lynparza.
• A more effective treatment
  • Patients who received Lynparza and chemotherapy (with a 48-hour gap) before surgery lived longer than patients who received chemotherapy only before surgery.
    • At 36 months, everyone who received Lynparza and chemotherapy was still alive compared to 88% of the group who received chemotherapy only.
• Longer time without cancer returning
  • Patients who received Lynparza and chemotherapy before surgery had more time without cancer worsening than those who received chemotherapy alone.
    • Among people treated with the combined therapy, 96% had no signs of cancer compared to 80% with chemotherapy alone.
• Reconsidering how success of neoadjuvant therapy is measured
  • The percentage of people whose cancer is no longer detectable before their scheduled surgery (pathological complete response, pCR) is often used to judge how well a neoadjuvant therapy works. In this study, pCR did not accurately predict patients’ survival.

• Side effects varied
  • People who received Lynparza 48 hours after starting chemotherapy had fewer severe bone marrow problems compared to people on other schedules.
  • Participants receiving Lynparza and chemotherapy together were more likely to experience moderate to serious side effects (grade 3 or higher) than those receiving chemotherapy alone (77% versus 60%).
  • The most common side effect with the combined therapy was low blood cell counts.
  • About the same number of people in both study groups (those who received Lynparza and chemotherapy together, and those who received chemotherapy only) stopped treatment due to side effects.
  • Quality of life was similar in both study groups.

What does this mean for me?

This study shows that changing the amount and timing of cancer treatment can lead to a safer and more tolerable combined therapy.

If you have early-stage breast cancer and a BRCA1 or BRCA2 genetic mutation, these findings show that Lynparza plus chemotherapy  (given before surgery with a 48-hour gap) can lengthen survival compared to chemotherapy alone. Lynparza plus chemotherapy given before surgery with a 48-hour gap caused manageable side effects compared to giving these drugs at the same time.

The results of this study are promising but still need to be confirmed by a larger study. The combined therapy may be offered through a clinical trial before becoming standard care.

Reference

Abraham JE, O’Connor LO, Grybowicz L, et al. Neoadjuvant PARP inhibitor scheduling in BRCA1 and BRCA2 related breast cancer: PARTNER, a randomized phase II/III trial. Nature Communications. 2025; 16 (4269).
 

Disclosure: FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to ensure scientific integrity.

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Posted 8/31/25