The basal-like subtype of breast cancer shares many genetic features with high-grade serous ovarian cancer. These findings suggest that these two cancers are of similar molecular origin, so it may facilitate comparing therapeutic data for subtypes of breast and ovarian cancers.
The Cancer Genome Atlas (TCGA) research study described new insights into the four standard molecular subtypes of breast cancer. The four primary subtypes of breast cancer are HER2-enriched, luminal A, luminal B, and basal-like. The basal-like subtype has been called triple-negative breast cancer because many basal-like tumors, though not all, are negative for the estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2).
To obtain the insights into the subtypes, samples from 825 breast cancer patients were characterized. Subsets of tumors were examined for defects in DNA, RNA, and proteins through six different technologies. All six technologies were used to analyze nearly 350 tumors.
Marked genomic similarities were uncovered between the basal-like subtype and serous ovarian cancer. Both cancer types had largely the same mutation spectrum, meaning the types and frequencies of genomic mutations. Several additional common genomic features were identified, such as gene mutation frequency, which suggested that diverse genomic aberrations can converge into a limited number of cancer subtypes.
Basal-like tumors account for about 10% of all breast cancers and disproportionately affect younger women and those who are African American. These tumors are often aggressive and do not respond to therapies that target hormone receptors or standard chemotherapies.
In general, compared to the other subtypes, basal-like and HER2 tumors had the highest mutation rates but the shortest list of significantly mutated genes. These genes are thought to be the major drivers of cancer progression. Among the basal-like tumors, 80% had mutations in TP53 and about 20% had mutations in BRCA1 or BRCA2. Ovarian cancer also has a high frequency of TP53 mutations.
New drug targets for basal-like tumors are critically needed. The research suggests that patients with mutations in BRCA genes may benefit from PARP inhibitors or platinum-based chemotherapy, which are already used to treat ovarian cancer.
“Now, we’re much closer to understanding the true origins of the different types of breast cancer,” said the study coleader, Matthew J. Ellis, MD, PhD of Washington University School of Medicine in St. Louis. “With this information, physicians and scientists can look at their own samples to correlate patients’ tumor profiles with treatment response and overall outcomes. That’s the challenge for the future—translating a patient’s genetic profile into new treatment strategies.”
This research was published in Nature (2012;490:61-70).