Breast cancer survivors
Men with breast cancer
People with a genetic mutation linked to cancer risk
Triple negative breast cancer
Women under 45
Women over 45
Other mutations: people with BRCA mutations
Special populations: People with early stage breast cancer prior to surgery
The PARP inhibitor talazoparib (Talzenna) has been useful for treatment of advanced or metastatic breast cancer for patients with BRCA mutations. A preliminary study showed that the majority of patients who took talazoparib alone before surgery for early-stage breast cancer had effective treatment and manageable side effects. Expanded clinical trials are in progress to verify this result. (10/4/19)
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|Clinical trials||Resources and references|
|Questions for your doctor|
Whether the PARP inhibitor Talzenna (talazoparib) is effective for treating patients with early-stage cancer that can be surgically removed in patients with hereditary BRCA mutations.
Treating breast cancer before surgery (also known as neoadjuvant therapy) is used to reduce the size of the tumor and the risk of cancer recurrence. PARP inhibitors are a type of targeted therapy that has been approved for treating metastatic breast cancer in people with BRCA mutations. This study is one of the first to test whether a PARP inhibitor used alone (without chemotherapy) before surgery is effective for treatment of early-stage breast cancer.
This pilot study included 20 patients. The goal was to test the effectiveness and side effects of Talzenna (talazoparib) alone when taken for 6 months before surgery in patients with stage I, II or III breast cancer who had a hereditary BRCA mutation.
The majority of patients treated with talazoparib (Talzenna) before surgery had a pathologic complete response [pCR]), meaning that they had no detectable cancer in their breast or lymph nodes at the time of surgery. The study measured residual cancer burden (RCB), the amount of tumor that remains after treatment.
The side effects observed were tolerable tor most patients.
Two PARP inhibitors are approved in the U.S. to treat advanced breast and several others for ovarian cancer. As of now, no PARP inhibitors have been approved for early-stage breast cancer. Ongoing clinical trials are looking at the effectiveness and safety of these drugs for people in this population.
More research on talazoparib (Talzenna) as a treatment for early-stage breast cancer is needed to determine if this initial study result can be confirmed.
If you have metastatic breast cancer and have a BRCA mutation, you might consider discussing PARP inhibitor treatment with your health care provider.
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The following clinical trials are looking at effectiveness and/or safety of PARP inhibitors for early-stage breast cancer treatment:
The following trials are looking at PARP inhibitors for metastatic breast cancer:
Med News Today
The Oncology Learning Network
PARP inhibitors block the function of a DNA repair enzyme in cells. Tumor cells of people with inherited BRCA mutations or tumor cell that have acquired a BRCA mutation can be specifically targeted and destroyed by PARP inhibitors.
Two PARP inhibitors, olaparib (Lynparza) and talazoparib (Talzenna) are approved for treatment of advanced or metastatic breast cancers for people with an inherited mutation in one of the BRCA genes. The OlympiAD trial of olaparib (Lynparza) and the EMBRACA trial of talazoparib (Talzenna) showed that treatment with these drugs lengthened the time until tumors grew and improved quality of life among metastatic breast cancer patients compared to patients treated with chemotherapy.
Since PARP inhibitors are useful for treating metastatic breast cancer patients, can they be used to treat earlier-stage breast cancer? Typically, patients with BRCA-positive, early-stage tumors have been treated with chemotherapy before or at the time of surgery, which improved outcomes, specifically by increasing the frequency of pathologically complete recovery (pCR) or the frequency of clinically undetectable cancer.
The I-SPY trial found improved outcomes when the PARP inhibitor velociparib was given with traditional chemotherapy (carboplatin plus paclitaxel) compared to another chemotherapy combination. Other combination trials with PARP inhibitors for early-stage breast cancer have not shown any improved outcomes; however, in these studies, most participants did not have BRCA mutations. If PARP inhibitors work predominantly in people with BRCA mutations this may have confused the results.
Could PARP inhibitors alone give a similar or better result than chemotherapy drugs for people with BRCA mutations? Researchers at MD Anderson Cancer Center at the University of Texas tested whether tumors of patients with stage I to III breast cancer responded to the PARP inhibitor talazoparib (Talzenna) when it was given before other chemotherapy. Patients with BRCA mutations and stage I to III breast cancer who were treated with talazoparib for 2 months and then chemotherapy prior to surgery showed a decrease in tumor size.
This result led to this pilot study that looked at whether talazoparib by itself at the time of surgery improved patient outcomes with tolerable side effects.
whether patients with inherited BRCA mutations who were treated with talazoparib (Talzenna) alone for 6 months prior to surgery had undetectable tumors (a pathological complete response) and manageable side effects when compared to patients who were treated with other chemotherapy prior to surgery.
Participants were 20 patients with a verified inherited BRCA1 or BRCA2 mutation, stage I to III breast cancer, and a primary tumor of 1 cm or larger that was imaged by mammogram and ultrasound. Participants were enrolled from August 2016 to September 2017, with a median age of 38 years (range: 23 to 58 years). Although both men and women were eligible, all 20 participants were women. Among the participants:
Patients with HER2+ tumors were excluded. Patients were also excluded if they had previous surgery, radiation, or systemic therapy for breast cancer. Patients with prior ductal carcinoma in situ or who had treatment for a previous non-breast cancer at least 5 years prior were still eligible.
This pilot study of 20 patients intended to collect preliminary data to demonstrate the usefulness of a larger trial.
Twenty patients underwent a pretreatment biopsy, then took 1 mg of talazoparib once a day for 6 months, had surgery to remove their tumors and then had postsurgery treatment of their physician’s choice. The study measured residual cancer burden (RCB) or the amount of tumor that remains after treatment and tracked side effects among participants. Patients who had at least 4 months of talazoparib treatment and surgery within 6 weeks of their last dose were evaluated. One patient received 5 months of therapy, but had an enlarged lymph node and chose to have systemic chemotherapy before surgery. Her information was included for toxicity but not for the primary end point of pathologic response.
The majority of patients treated with talazoparib (Talzenna) before surgery had a pathologic complete response [pCR]) or no invasive disease in breast and lymph at the time they were evaluated. The study measured residual cancer burden (RCB), the amount of tumor that remains after treatment. A RBC-0 is the same as pathologic complete response. Residual cancer burden of 1 (RCB-1) or more have increasing amounts of tumor remaining.
The toxic side effect observed were tolerable tor most patients.
The most common less severe side effects were nausea, fatigue, anemia (low red blood cell count), hair loss, dizziness and breathing difficulties.
The most common severe side effects were anemia and nausea:
This trial had many limitations:
In this pilot study, Talzenna (talazoparib) alone appears to be a promising treatment for patients with BRCA mutations who develop early-stage breast cancer. An expanded clinical trial with a larger number of participants is needed to determine if this treatment approach is viable.
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