Association of molecular subtypes with breast cancer risk factors

Abstract

As breast cancer (BC) screening identifies many BCs with a good prognosis, which might be overdiagnosed and therefore overtreated, the identification of subgroups with a high risk for aggressive subtypes might be helpful. The aim of this case-case analysis was to investigate the association between epidemiological risk factors and molecular subtypes in a cohort of BC patients. Epidemiological risk factors for 2587 BC patients were obtained using a structured questionnaire and from the patients' charts. The histopathological information (estrogen and progesterone receptor, HER2 and Ki-67) used in the analysis was retrieved from the original pathology reports. Analyses using conditional inference regression trees were carried out on these data. The strongest influence factor on the distribution of the molecular subtypes was age at first diagnosis of BC. An influence of BMI was also identified in patients aged either more than 42 years or 49.6 years or less. Older patients aged more than 49.6 years and perimenopausal women with a BMI of 32.4 kg/m or less were most likely to develop luminal A-like BC. Young patients aged 42 years or less and perimenopausal patients with a BMI more than 32.4 kg/m more often developed triple-negative BC. The study confirmed that age at diagnosis is an important factor influencing the distribution of molecular subtypes. In the perimenopausal group, it may be postulated that BMI plays a critical role in the pathogenesis of BC, defining a subgroup that is more likely to develop triple-negative BC or luminal B-like disease and another group in which there is a more postmenopausal distribution pattern.

Prognostic impact of breast cancer subtypes in elderly patients

“…In contrast to younger patients, the most frequently observed subtype in this large cohort of elderly patients was by far the luminal subtype followed by HER2-positive and triple-negative disease. These data are well in line with other studies showing that the incidence of luminal BC is increasing with age [ 26 , 27 ]. Still, unfavourable tumour phenotypes such as HER2-positive and TNBC are observed in patients ≥70 years of age as well [ 12 ], necessitating specific age-adapted treatment approaches.…”

Etiology of hormone receptor positive breast cancer differs by levels of histologic grade and proliferation

“…luminal A and luminal B subtypes . Epidemiological studies suggest that these two subtypes could have differential associations with risk factors . However, although correlated, histologic grade and KI67 reflect different biological features of tumors that could be of etiological relevance.…”

“…[13][14][15] Epidemiological studies suggest that these two subtypes could have differential associations with risk factors. 10,16 However, although correlated, histologic grade and KI67 reflect different biological features of tumors that could be of etiological relevance. Unlike grade which encompasses both differentiation and proliferation, KI67 is expressed only during the proliferative phases of the cell-cycle and is one of the most commonly used markers of proliferation.…”

Alcohol, Physical Activity, Smoking, and Breast Cancer Subtypes in a Large, Nested Case–Control Study from the Norwegian Breast Cancer Screening Program

“…Alcohol consumption, physical activity, and smoking are modifiable risk factors that have been associated with breast cancer overall to some or larger degree (4)(5)(6). Several studies have investigated the association between alcohol (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), smoking (14,(19)(20)(21)(22)(23)(24)(25), physical activity (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), and subtypes of breast cancer. A large meta-analysis suggested stronger positive associations between alcohol and estrogen receptor (ER)-positive tumors and weaker positive associations between alcohol and ER-negative tumors (18).…”