Abstract 1747: Relationships between anthropometric and reproductive factors and risks of triple-negative and HER2-overexpressing breast cancers
Authors: Li Christopher I. , Chen Lu , Tang Mei-Tzu , Porter Peggy , Cook Linda 
Published: July 2016

Background: Triple negative (TN, do not express estrogen receptor (ER), progesterone receptor (PR), or HER2) and HER2-overexpressing (H2E, ER-/HER2+) tumors are two particularly aggressive molecular subtypes of breast cancer that disproportionately impact young women. There is still lack of knowledge on factors influencing etiologies of these cancers and how these relationships may vary between premenopausal and postmenopausal women.

Methods: We conducted a population-based case-case study of women 20 to 69 years of age diagnosed with invasive breast cancer while living in the Seattle, WA or Albuquerque, NM areas between 2004 and 2012. It included four case groups defined based on joint ER/PR/HER2 status: TN (n = 1,294), H2E (n = 489), luminal A (ER+/HER2-, n = 778) and luminal B (ER+/HER2+, n = 131). Medical records were reviewed at both study sites to ascertain information on risk factors at the time of breast cancer diagnosis, supplemented with data from telephone interviews (Seattle cases only). Polytomous logistic regression was used to estimate the odds ratio (OR) and associated 95% confidence intervals (CIs) for TN, H2E, and luminal B breast cancers relative to luminal A cancers and various risk factors including body mass index (BMI), ever having a full term pregnancy, number of full term pregnancies, and age at first birth.

Results: Obese pre-menopausal women (BMI≥30 kg/m2) had an 82% (95% CI: 1.32-2.51) increased risk of TN breast cancer compared to normal weight women (BMI&lt;25 kg/m2), and those in the highest weight quartile had a 78% (95% CI: 1.21-2.60) increased risk of TN disease compared to those in the lowest quartile. In contrast, among post-menopausal women obesity was associated with reduced risks of both TN (OR = 0.72, 95% CI: 0.53-0.98) and H2E (OR = 0.47, 95% CI: 0.32-0.68) cancers. Earlier age at first full-term pregnancy and age at menopause were positively associated with risk of TN breast cancer (p-values for trend: 0.003 and 0.024, respectively). Parity was associated with a 43% (95% CI: 1.08-1.89) elevated risk of H2E breast cancer, and women who had ≥3 full-term pregnancies had a 63% (95% CI: 1.16-2.29, p-trend: 0.013) increased risk of this subtype. Breastfeeding for ≥36 months was associated with a 3.47-fold (95% CI: 1.17-10.33) increased risk of luminal B breast cancer, but a 49% (95% CI: 0.27-0.99) lower risk of TN breast cancer.

Conclusion: This large population-based study adds to evidence that anthropometric and reproductive factors have divergent impacts on risk of aggressive subtypes of breast cancer. The higher incidence rates of TN cancers observed among certain populations, such as younger African American and Hispanic women in the United States, may be due in part to these relationships. Given the poorer prognoses of these aggressive breast cancer subtypes, clarifying the impact of potentially modifiable factors on their risks is of great public health importance.

Citation Format: Christopher I. Li, Lu Chen, Mei-Tzu Tang, Peggy Porter, Linda Cook. Relationships between anthropometric and reproductive factors and risks of triple-negative and HER2-overexpressing breast cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1747.