Response to Chemotherapy Before Breast Cancer Surgery Varies by Race
The way a breast cancer responds to chemotherapy before surgery is influenced by the genetics of the tumor, which varies by race. A study suggests that these genetic differences may be part of the reason why Black women are more likely to die from breast cancer than white women.
The research was published online on March 30, 2023, by the journal JAMA Network Open. Read “Racial Disparities in Pathological Complete Response Among Patients Receiving Neoadjuvant Chemotherapy for Early-Stage Breast Cancer.”
Doctors call treatments given before surgery neoadjuvant treatments. So doctors call chemotherapy given before surgery neoadjuvant chemotherapy.
Why neoadjuvant chemotherapy?
Doctors may prescribe chemotherapy before surgery to remove early-stage breast cancer to shrink or lower the cancer stage. A smaller cancer may make it possible for a surgeon to remove a previously inoperable tumor with surgery or allow a woman to have lumpectomy rather than mastectomy, if she would like.
One way doctors judge the effectiveness of neoadjuvant treatments is by looking for any actively growing cancer cells in tissue removed during surgery. If there aren’t any cancer cells in the tissue, doctors call it a pathologic complete response or pCR. If there are cancer cells in the tissue, doctors call it residual cancer.
Many studies show that people who have pCR after neoadjuvant chemotherapy usually need fewer treatments after surgery and, importantly, have better outcomes, including survival.
About the study
Although Black women are more likely to die from breast cancer than women of other races and ethnicities, research results have been mixed on racial disparities in pCR rates based on the characteristics of the breast cancer.
In this University of Chicago study, the researchers wanted to look at pCR rates based on the genetics of breast cancer tumors by subtypes, as well as by the race and ethnicity of the women diagnosed.
The study included 690 women diagnosed with early-stage breast cancer at the University of Chicago Medical Center between 2002 and 2020. All the women received neoadjuvant chemotherapy. The researchers followed half the women for more than 5.4 years and half for shorter periods of time.
Among the women in the study:
269 were Black
355 were white
35 were Asian
30 were Hispanic
one was American Indian or Alaska Native
Among the Black women in the study:
38.7% were diagnosed with triple-negative breast cancer
29% were diagnosed with hormone receptor-positive, HER2-negative breast cancer
19.7% were diagnosed with hormone receptor-positive, HER2-positive breast cancer
12.6% were diagnosed with hormone receptor-negative, HER-positive breast cancer
60.2% were diagnosed with stage II breast cancer
29.7% were diagnosed with stage III breast cancer
10% were diagnosed with stage I breast cancer
13.8% had two or more other health conditions
20.8% had more than an eight-week delay before starting chemotherapy
48.7% had private insurance
32.1% had Medicaid
19.2% had Medicare
Among the white women in the study:
35.5% were diagnosed with hormone receptor-positive, HER2-negative breast cancer
32.7% were diagnosed with triple-negative breast cancer
20% were diagnosed with hormone receptor-positive, HER2-positive breast cancer
11.8% were diagnosed with hormone receptor-negative, HER2-positive breast cancer
58.6% were diagnosed with stage II breast cancer
23.9% were diagnosed with stage III breast cancer
17.5% were diagnosed with stage I breast cancer
5.1% had two or more other health conditions
11% had more than an eight-week delay before starting chemotherapy
82.6% had private insurance
13.1% had Medicare
4.3% had Medicaid
The researchers noted that there were no differences in the treatment regimens of Black and white women.
The researchers looked at pCR rates and found that:
36.6% of the white women had a pCR
28.6% of the Black women had a pCR
Compared with white women, Black women were:
less likely to have a pCR
more likely to be diagnosed with higher stage breast cancer
more likely to have other health conditions
more likely to have a delay of more than eight weeks before starting chemotherapy
more likely to have Medicaid insurance
The researchers’ analysis showed that having a pCR was linked to better survival. Women who didn’t have a pCR were six times more likely to die from breast cancer and six times more likely to have the breast cancer come back (recurrence) than women who had a pCR.
Several factors were linked to being less likely to have a pCR:
being diagnosed with hormone receptor-positive, HER2-negative breast cancer
being diagnosed with breast cancer at an older age
being diagnosed with a higher stage of breast cancer
having a longer delay before starting chemotherapy
The researchers then looked at pCR rates by race and breast cancer subtype.
Among women diagnosed with hormone receptor-positive, HER2-negative breast cancer:
20.5% of the Black women had a pCR
19.8% of the white women had a pCR
Among women diagnosed with hormone receptor-positive, HER2-positive breast cancer:
24.5% of the Black women had a pCR
38% of the white women had a pCR
Among women diagnosed with hormone receptor-negative, HER2-positive breast cancer:
41.2% of the Black women had a pCR
73.8% of the white women had a pCR
Among women diagnosed with triple-negative breast cancer:
32.7% of the Black women had a pCR
40.5% of the white women had a pCR
The researchers also analyzed the genetics of the original breast cancer and the residual cancer.
Overall, the genetic mutations in the residual cancer were different from the mutations in the original cancer:
The FGF4, FGF3, and CCND1 genes were overexpressed more often in the residual cancers than in the original cancers. These genes help control how cells grow and divide.
The original cancers had more genetic mutations in them than the residual cancers.
The researchers also found that Black women diagnosed with HER2-positive breast cancer were more likely to have alterations in the MAPK and PI3K/AKT pathways:
30% of the HER2-positive breast cancers in Black women had MAPK pathway mutations
4.6% of the HER2-positive breast cancers in white women had MAPK pathway mutations
45% of the HER2-positive breast cancers in Black women had PI3K/AKT pathway mutations
18.2% of the HER2-positive breast cancers in white women had PI3K/AKT pathway mutations
Mutations in the MAPK and PI3K/AKT pathways are linked to cancers being resistant to anti-HER2 medicines.
“We observed that the racial disparity in pCR was most profound among patients with [hormone receptor-negative, HER2-positive] disease,” the researchers wrote. “Given that pCR rate for women with [hormone receptor-negative, HER2-positive] disease was also highest of all breast cancer subtypes, as shown in this and other studies, disparate response to similar treatment plans suggested the existence of underexplored biological differences.
“ . . . this study identified that alterations in two pathways, MAPK and PI3K/AKT, occurred more frequently among Black patients with [HER2-positive] disease compared with white patients,” they continued. “Alterations in these two pathways were previously reported to result in resistance to anti-[HER2] therapy. On the other hand, they also have the potential to serve as viable therapeutic targets to be combined with anti-[HER2] therapies.”
What this means for you
For the last four decades, we’ve known that Black women are about 40% more likely to die from breast cancer than white women. Studies have suggested that a number of factors contribute to this disparity, including structural racism in the healthcare system and the biology of the cancer tumor.
More recent research suggests that social determinants of health — conditions in the environments where people live — contribute as much to breast cancer survival differences between Black and white women as the characteristics of the cancer.
Many scientists are working to close this survival gap, but because so many factors seem to contribute to the disparity, much more research is needed. We need a better understanding of how the multi-layered effects of social and economic disadvantage affect cancer care, as well as more research on the biology of breast cancer tumors in Black women to understand why these tumors are more aggressive.
All people — no matter their race, ethnicity, gender identity, sexual orientation, age, economic status, or other health conditions — deserve the best breast cancer care possible. Differences that affect outcomes, such as access to care, and quality and consistency of care, should be eliminated.
— Last updated on June 5, 2023 at 1:20 PM