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Breast cancer mortality among younger women varies by subtype
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A breast cancer diagnosis at age 40 years or younger corresponded with a higher mortality risk, especially among women with luminal tumors, according to research published in Journal of Clinical Oncology.
“Numerous studies have documented that young women are more likely to develop more aggressive subtypes of breast cancer with unfavorable prognostic features, as well as present with more advanced-stage disease,” Ann H. Partridge, MD, MPH, associate professor of medicine at Harvard Medical School and founder and director of the Program for Young Women with Breast Cancer at Dana-Farber Cancer Institute, and colleagues wrote. “A majority of tumors in all age groups are hormone receptor–positive and [HER-2–negative], but compared with tumors in older women, those in young women are more likely to be high grade, be hormone receptor–negative, have high proliferation fraction, and exhibit lymphovascular invasion.”
Partridge and colleagues evaluated data from 17,575 women treated for newly diagnosed stage I to stage III breast cancer at one of eight institutions participating in the National Comprehensive Cancer Network Breast Cancer Outcomes Database Project.
Of these, 1,916 women were aged 40 years or younger at diagnosis (mean age, 35 years).
Median follow-up was 6.4 years.
Younger women diagnosed with breast cancer were more likely to be nonwhite, be premenopausal, have a higher education level, and be employed or enrolled in school (P < .001 for all). Younger women also were more likely to have higher-stage and -grade disease, and their tumors were more likely to be of luminal B, triple-negative or HER-2 subtype (P < .001 for all).
A multivariate analysis found that women aged 40 years or younger had a 90% higher likelihood of dying of breast cancer than women aged 51 to 60 years (HR = 1.9; 95% CI, 1.6-2.3).
Adjustment for potentially influential variables — such as treatment, stage at diagnosis, tumor grade and year of diagnosis — revealed a 50% higher likelihood of death for the younger age group (HR = 1.5; 95% CI, 1.3-1.8).
Fully adjusted models showed no survival differences among women aged 41 to 50 years (HR = 0.9; 95% CI, 0.8-1.1); 61 to 70 years (HR = 0.8; 95% CI, 0.7-1); or older than 70 years (HR = 1; 95% CI, 0.7-1.4) compared with women aged 51 to 60 years.
An analysis based on tumor subtype showed younger women with luminal A tumors were twice as likely to die of breast cancer than women aged 51 years to 60 years (HR = 2.1; 95% CI, 1.4-3.2).
A greater mortality risk also occurred among younger women with luminal B disease (HR = 1.4; 95% CI, 1.1-1.9), and a borderline increased risk occurred among younger women with triple-negative breast cancer (HR = 1.4; 95% CI, 1-1.8).
In contrast, younger women with HER-2–positive breast cancer did not have a significantly increased risk for death after controlling for potential confounders (HR = 1.2; 95% CI, 0.8-1.9).
younger women with luminal B tumors suggested the increased risk for death primarily occurred in the HER-2–negative subgroup. The prognostic effect among younger women appeared to primarily occur in women with luminal A tumors after the researchers controlled for detection method.
The researchers identified several potential limitations. Because the NCCN database only enrolled patients from large comprehensive cancer centers, these data may not be representative of the overall population of women with breast cancer.
Additionally, the researchers acknowledged a potential for bias, as women with more aggressive tumors may choose treatment at a comprehensive cancer center or academic medical center.
“[T]his study supports the growing evidence that the relationship between age at diagnosis and breast cancer–specific survival varies by tumor subtype, which has implications for both treatment decisions and future research directions,” Partridge and colleagues wrote. “Further research to elucidate differences in breast cancer biology and efficacy of therapy among young women with luminal breast cancer by age may identify targets to improve outcomes in this higher-risk population.” – by Cameron Kelsall
Disclosure: Partridge reports a consultant role with Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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