Breast Cancer Risk Factors and Survival by Tumor Subtype: Pooled Analyses from the Breast Cancer Association Consortium
Authors: Morra Anna , Jung Audrey Y. , Behrens Sabine , Keeman Renske , Ahearn Thomas U. , Anton-Culver Hoda , Arndt Volker , Augustinsson Annelie , Auvinen Päivi K. , Beane Freeman Laura E. , Becher Heiko , Beckmann Matthias W. , Blomqvist Carl , Bojesen Stig E. , Bolla Manjeet K. , Brenner Hermann , Briceno Ignacio , Brucker Sara Y. , Camp Nicola J. , Campa Daniele , Canzian Federico , Castelao Jose E. , Chanock Stephen J. , Choi Ji-Yeob , Clarke Christine L. , Couch Fergus J. , Cox Angela , Cross Simon S. , Czene Kamila , Dörk Thilo , Dunning Alison M. , Dwek Miriam , Easton Douglas F. , Eccles Diana M. , Egan Kathleen M. , Evans D. Gareth , Fasching Peter A. , Flyger Henrik , Gago-Dominguez Manuela , Gapstur Susan M. , García-Sáenz José A. , Gaudet Mia M. , Giles Graham G. , Grip Mervi , Guénel Pascal , Haiman Christopher A. , Håkansson Niclas , Hall Per , Hamann Ute , Han Sileny N. , Hart Steven N. , Hartman Mikael , Heyworth Jane S. , Hoppe Reiner , Hopper John L. , Hunter David J. , Ito Hidemi , Jager Agnes , Jakimovska Milena , Jakubowska Anna , Janni Wolfgang , Kaaks Rudolf , Kang Daehee , Kapoor Pooja Middha , Kitahara Cari M. , Koutros Stella , Kraft Peter , Kristensen Vessela N. , Lacey James V. , Lambrechts Diether , Le Marchand Loic , Li Jingmei , Lindblom Annika , Lubiński Jan , Lush Michael , Mannermaa Arto , Manoochehri Mehdi , Margolin Sara , Mariapun Shivaani , Matsuo Keitaro , Mavroudis Dimitrios , Milne Roger L. , Muranen Taru A. , Newman William G. , Noh Dong-Young , Nordestgaard Børge G. , Obi Nadia , Olshan Andrew F. , Olsson Håkan , Park-Simon Tjoung-Won , Petridis Christos , Pharoah Paul D.P. , Plaseska-Karanfilska Dijana , Presneau Nadege , Rashid Muhammad U. , Rennert Gad , Rennert Hedy S. , Rhenius Valerie , Romero Atocha , Saloustros Emmanouil , Sawyer Elinor J. , Schneeweiss Andreas , Schwentner Lukas , Scott Christopher , Shah Mitul , Shen Chen-Yang , Shu Xiao-Ou , Southey Melissa C. , Stram Daniel O. , Tamimi Rulla M. , Tapper William , Tollenaar Rob A.E.M. , Tomlinson Ian , Torres Diana , Troester Melissa A. , Truong Thérèse , Vachon Celine M. , Wang Qin , Wang Sophia S. , Williams Justin A. , Winqvist Robert , Wolk Alicja , Wu Anna H. , Yoo Keun-Young , Yu Jyh-Cherng , Zheng Wei , Ziogas Argyrios , Yang Xiaohong R. , Eliassen A. Heather , Holmes Michelle D. , García-Closas Montserrat , Teo Soo Hwang , Schmidt Marjanka K. , Chang-Claude Jenny 
Published: January 2021

Abstract

Background:
It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype.

Methods:
We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype.

Results:
There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj &gt; 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus &lt;20 years at first pregnancy [0.79 (0.72–0.86)]; &gt;0–&lt;5 years versus ≥10 years since last full-term birth [1.31 (1.11–1.55)]; ever versus never use of oral contraceptives [0.91 (0.87–0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen–progestin therapy [0.61 (0.54–0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02–1.21) for current versus never smoking.

Conclusions:
We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype.

Impact:
Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.