Age-Specific Changes in Intrinsic Breast Cancer Subtypes: A Focus on Older Women

Abstract

Purpose. Breast cancer (BC) is a disease of aging and the number of older BC patients in the U.S. is rising. Immunohistochemical data show that with increasing age, the incidence of hormone receptor-positive tumors increases, whereas the incidence of triple-negative tumors decreases. Few data exist on the frequency of molecular subtypes in older women. Here, we characterize the incidence and outcomes of BC patients by molecular subtypes and age. Patients and Methods. Data from 3,947 patients were pooled from publicly available clinical and gene expression microarray data sets. The PAM50 algorithm was used to classify tumors into five BC intrinsic subtypes: luminal A, luminal B, HER2-enriched, basal-like, and normal-like.The association of age and subtype with recurrence-free survival (RFS), overall survival, and disease-specific survival (DSS) was assessed.Results. The incidence of luminal (A, B, and A1B) tumors increased with age (p , .01, p , .0001, and p , .0001, respectively), whereas the percentage of basal-like tumors decreased (p , .0001). Among patients 70 years and older, luminal B, HER2-enriched, and basal-like tumors were found at a frequency of 32%, 11%, and 9%, respectively. In older women, luminal subtypes had better outcomes than basal-like and HER2-enriched subtypes. After controlling for subtype, treatment, tumor size, nodal status, and grade, increasing age had no impact on RFS or DSS. Conclusion. More favorable BC subtypes increase with age, but older patients still have a substantial percentage of high-risk tumor subtypes. After accounting for tumor subtypes, age at diagnosis is not an independent prognostic factor for outcome. The Oncologist 2014;19:1076-1083 Implications for Practice: Breast cancer incidence increases dramatically with age, and the number of older patients is increasing worldwide. Estrogen receptor, progesterone receptor, and HER2 expression remain the cornerstones for selecting adjuvant systemic therapy, but an expanding body of knowledge suggests that making decisions on the basis of the genetic characteristics of the breast cancer (molecular subtypes) may ultimately improve on current treatment outcomes. Our data suggest that although increasing age is associated with more favorable breast cancer biology, within subtypes outcomes are similar for all age groups. Also, after accounting for breast cancer subtypes, age alone was not related to outcome.

The prognostic impact of age in different molecular subtypes of breast cancer

“…1a). According to a recent large microarray study, increasing age at diagnosis was not associated with patients' prognosis after stratification for clinical/pathological variables including breast cancer subtype [20]. Nevertheless, when we controlled for subtype composition and clinical variables in multivariate analysis, we still detected a significant prognostic effect of young age (P = 0.012, Table 2).…”

“…One large study based on microarray data from 3522 breast cancers reported a prognostic value of age independent of molecular subtypes in multivariate analysis [4]. However, very recently, another large microarray study (n = 3947) concluded that the prognostic effect of age is based only on differences in subtype composition [20]. We had previously performed a study on age based on clinical and pathological data.…”

Breast Cancer beyond the Age of Mutation

“…A full 80% of breast cancers in women over 50 are the luminal subtypes [9]. There are no particular patterns of gene mutations in these age-related cancers, but rather, they have the greatest transcriptional diversity and their transcriptomes exhibit age-specific expression patterns [10,11].…”

4th Symposium on Primary Breast Cancer in Older Women. Theme: Putting Personalized Care Into Practice (Held: 3 March 2017)

“…The stark differences in the biology of breast cancer was displayed on one slide [4,5]. According to standard pathology reports, more luminal cases are seen in older women; on the molecular levels it is apparent that less aggressive or basal-type cases are also seen in older women.…”

“…Dr Brain explained that although there have been great strides in the past decade in cancer management in general, this has not benefited the entire population, with older persons deriving less benefit overall. The main dilemma faced when approaching any cancer in the older patient is ageism -when you decide not to treat as you consider the patient is too old -referred to as 'therapeutic nihilism', and the opposite also can be true -'blind therapeutic enthusiasm' -the use of new treatment innovations bringing futile benefits with potential and uncontrolled side effects.The stark differences in the biology of breast cancer was displayed on one slide [4,5]. According to standard pathology reports, more luminal cases are seen in older women; on the molecular levels it is apparent that less aggressive or basal-type cases are also seen in older women.…”