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There are various types of systemic therapies, including chemotherapy, hormonal therapy, anti-HER2 therapy, immunotherapy, and targeted therapy. Systemic therapies can be infused intravenously, given as injections or taken orally, and may be given after surgery (adjuvant therapy) or before surgery (neo-adjuvant or pre-operative therapy). Neo-adjuvant therapies are becoming more common, in part because they allow physicians to see whether or not the tumor responds to a certain treatment before surgery.
Treatment depends on type of cancer and prognostic markers
The specific therapy patients receive depends upon the “prognostic markers” that are present in a tumor. These markers include the estrogen receptor (ER), progesterone receptor (PR), and HER2.
Prognostic markers are assessed in every case of invasive breast cancer. For example:
Our cells use BRCA1 and BRCA2 genes to repair damage to our DNA. However, BRCA-mutation carriers may have difficulty repair some types of DNA damage – in either regular cells or cancer cells.
Certain chemotherapy drugs, including the platinum drugs carboplatin and cisplatin, may be more effective against BRCA-associated cancers because the drugs work by damaging the DNA in cancer cells. This process takes advantage of BRCA-mutation carriers’ existing inability to repair DNA, causing cancer cells to die from excessive DNA damage.
Currently, platinum therapies are used as a standard first-line treatment for ovarian cancer, and researchers are looking at whether these same treatments may be effective for newly diagnosed breast cancer patients with mutations in BRCA.
A previous small clinical trial assessed the activity of the platinum-based drug cisplatin alone in a small group of BRCA1 carriers with newly diagnosed early stage breast cancer. Cisplatin was given for four cycles before surgery and when those 25 patients had their surgeries, in 72% of them, their tumors were completely eradicated from their breast and lymph nodes. This rate of complete response was much higher than that typically seen, and these data have led to further randomized studies.
A clinical trial – known as the INFORM study – currently is looking at whether newly-diagnosed breast cancer patients with BRCA mutations respond better to platinum therapy as compared with standard chemotherapy. Results of this study could help us better understand the best chemotherapy treatment for BRCA-associated cancers.
Results from the Triple-Negative Breast Cancer Trial (TNT), a phase III clinical trial that compared the platinum-based drug carboplatin to the drug docetaxel as first line treatment in 376 patients with metastatic triple-negative breast cancer and/or with a mutation in BRCA1 or BRCA2, were recently reported. (Patients with BRCA mutations and ER/PR positive breast cancer also were included in this study.) Researchers compared how well each drug worked in treating these advanced cancers. When they compared the two drugs in all patients, the response rate was similar, with 31.4% responding to carboplatin and 35.3% responding to docetaxel. However, when they examined the results for the 43 patients who had mutations in either BRCA1 or BRCA2, the researchers found that 68.0% of carriers responded to carboplatin as compared with 33.3% of carriers who received docetaxel. The results of this study strongly suggest that knowing the BRCA mutation status of patients with advanced triple negative breast cancer can be useful in determining which chemotherapy to use.