A promising new approach to targeted therapy may expand treatment options for some women with early-stage breast cancer associated with specific genetic mutations. (Cancers in the early stages have not spread to distant organs or tissues.)
What does the BRCA gene do?
You may have heard of the BRCA (BReast CAncer) gene family, which includes the BRCA1 and BRCA2 genes. Normally, BRCA genes contribute to the repair of DNA (genetic code) damage that occurs on a regular basis in cells throughout the human body.
BRCA mutations that are inherited are aberrant abnormalities in these genes that are handed down from parent to kid. When an individual carries a BRCA mutation, their body is unable to repair regular DNA damage to cells as easily. This cumulative damage to cells may contribute to the development of cancer. Having a BRCA1 or BRCA2 mutation — or both — increases a person's risk of developing breast, ovarian, prostate, or pancreatic cancer, as well as melanoma. Other gene alterations and other factors can also affect a person's risk of developing breast cancer.
In general, only about 3% to 5% of all women diagnosed with breast cancer have BRCA gene mutations. However, certain subgroups of people are more likely to have BRCA mutations, including those with triple-negative breast cancer (TNBC), Ashkenazi Jewish heritage, a significant family history of breast and/or ovarian cancer, and younger women with breast cancer.
Breast cancer types and inherited BRCA mutations
Breast cancers of specific types are frequently detected in women with BRCA gene mutations.
Estrogen receptor-positive, HER2-negative breast cancer: Women with a BRCA2 mutation are more likely to develop estrogen receptor-positive, HER2-negative breast cancer — that is, cancer cells that are fuelled by estrogen but not by a protein called HER2 (human epidermal growth factor 2).
Women with a BRCA1 mutation are more likely to develop triple-negative breast cancer (ER-/PR-/HER2-) – cancer cells that are not fuelled by estrogen, progesterone, or HER2.
Understanding what causes various types of breast cancer to grow aids scientists in developing new treatments and physicians in selecting available therapies to delay or stop tumor growth. Frequently, this will require a combination of treatments.
A new treatment option for early-stage breast cancers associated with BRCA mutations
Women with early-stage breast cancer and hereditary BRCA1/BRCA2 mutations were included in the Olympia trial. Despite normal treatment, all were at significant risk of breast cancer recurrence.
The study participants had received standard breast cancer treatment:
surgical procedure (a mastectomy or lumpectomy)
Chemotherapy (which may be administered before to or following surgery), radiation, and maybe a hormone-blocking medication called endocrine therapy.
They were randomly allocated to consume olaparib or a placebo (sugar tablets) twice daily for one year.
Olaparib is a member of a class of medications known as PARP inhibitors. PARP (poly adenosine diphosphate-ribose polymerase) is a typically occurring enzyme that aids in DNA repair. By inhibiting this enzyme in BRCA-mutated cancer cells, increasing DNA damage leads the cells to die.
The New England Journal of Medicine reported the study's findings. Women who got olaparib were less likely than those who received a placebo to have their breast cancer relapse or metastasis (spread to distant organs or tissues). After an average of two and a half years, slightly more than 85% of women who took olaparib were alive and had no recurrence of cancer or new second malignancy, compared to 77% of women given with placebo.
Additionally, the researchers calculated that after three years:
With olaparib, the probability of cancer not spreading to distant organs or tissues was roughly 88 percent, compared to 80 percent with placebo.
The olaparib-treated group had a 92 percent chance of survival, while the placebo group had an 88 percent chance of survival.
Olaparib may cause a decrease in white blood cell count, a decrease in red blood cell count, and fatigue. These were extremely unlikely to develop.
Olaparib has previously been licensed by the Food and Drug Administration for the treatment of BRCA-related ovarian, pancreatic, and prostate cancers, as well as metastatic breast cancer. FDA approval for BRCA-related early-stage breast cancer is expected soon, based on this study. These findings imply that continuing to take olaparib for a year following completion of normal therapy may be a suitable option for women with early-stage breast cancer who have a hereditary BRCA gene mutation and are at a high risk of cancer recurrence and, possibly, metastasis.