TY - JOUR
T1 - Breast cancer risk factors in relation to molecular subtypes in breast cancer patients from Kenya
AU - Sayed, Shahin
AU - Fan, Shaoqi
AU - Moloo, Zahir
AU - Wasike, Ronald
AU - Bird, Peter
AU - Saleh, Mansoor
AU - Shaikh, Asim Jamal
AU - Figueroa, Jonine D.
AU - Naidoo, Richard
AU - Makokha, Francis W.
AU - Gardner, Kevin
AU - Oigara, Raymond
AU - Njoroge, Faith Wambui
AU - Magangane, Pumza
AU - Mutebi, Miriam
AU - Chauhan, Rajendra
AU - Mwanzi, Sitna
AU - Govender, Dhirendra
AU - Yang, Xiaohong R.
N1 - Funding Information:
The current study was funded from the Deans Fund at Aga Khan University Hospital, Nairobi. The funding sponsor did not have any role in the design of the study and collection, analysis, and interpretation of data, and in writing the manuscript. The initial study was supported through the 2011-GSK-ERI/GlaxoSmithKline/International . The research was partially supported by the intramural research program of the Division of Cancer Epidemiology & Genetics, National Cancer Institute, USA.
Funding Information:
This study was nested within a previously completed breast cancer study from Kenya []. Ethics approval was provided by the Research Ethics Committees of the Aga Khan University Hospital Nairobi (2016/REC-32 (v3) and the Faculty of Health Sciences Research Ethics Committee of the University of Cape Town (HREC 427/2016). The study was also permitted by the National Commission for Science Technology and Innovation, Kenya (Ref No: NACOSTI/P/19/72237/28785), License number: NACOSTI/P/19/993).
Funding Information:
The authors would like to acknowledge Dr. Gretchen Gierach (Division of Cancer Epidemiology & Genetics, National Cancer Institute, USA) for her encouragement and support in the actualization of this manuscript, Angela Mutuku, Subash Govender, Johnstone Ngao, Raymond Kriel, and Veronica Ngundo for providing technical services. Permission to acknowledge all those mentioned in the Acknowledgements section was taken. JDF/SS/FM acknowledges funding from UKRI grant reference MR/S015027/1.
Publisher Copyright:
© 2021, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - Background: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. Methods: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. Results: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.
AB - Background: Few studies have investigated risk factor heterogeneity by molecular subtypes in indigenous African populations where prevalence of traditional breast cancer (BC) risk factors, genetic background, and environmental exposures show marked differences compared to European ancestry populations. Methods: We conducted a case-only analysis of 838 pathologically confirmed BC cases recruited from 5 groups of public, faith-based, and private institutions across Kenya between March 2012 to May 2015. Centralized pathology review and immunohistochemistry (IHC) for key markers (ER, PR, HER2, EGFR, CK5-6, and Ki67) was performed to define subtypes. Risk factor data was collected at time of diagnosis through a questionnaire. Multivariable polytomous logistic regression models were used to determine associations between BC risk factors and tumor molecular subtypes, adjusted for clinical characteristics and risk factors. Results: The median age at menarche and first pregnancy were 14 and 21 years, median number of children was 3, and breastfeeding duration was 62 months per child. Distribution of molecular subtypes for luminal A, luminal B, HER2-enriched, and triple negative (TN) breast cancers was 34.8%, 35.8%, 10.7%, and 18.6%, respectively. After adjusting for covariates, compared to patients with ER-positive tumors, ER-negative patients were more likely to have higher parity (OR = 2.03, 95% CI = (1.11, 3.72), p = 0.021, comparing ≥ 5 to ≤ 2 children). Compared to patients with luminal A tumors, luminal B patients were more likely to have lower parity (OR = 0.45, 95% CI = 0.23, 0.87, p = 0.018, comparing ≥ 5 to ≤ 2 children); HER2-enriched patients were less likely to be obese (OR = 0.36, 95% CI = 0.16, 0.81, p = 0.013) or older age at menopause (OR = 0.38, 95% CI = 0.15, 0.997, p = 0.049). Body mass index (BMI), either overall or by menopausal status, did not vary significantly by ER status. Overall, cumulative or average breastfeeding duration did not vary significantly across subtypes. Conclusions: In Kenya, we found associations between parity-related risk factors and ER status consistent with observations in European ancestry populations, but differing associations with BMI and breastfeeding. Inclusion of diverse populations in cancer etiology studies is needed to develop population and subtype-specific risk prediction/prevention strategies.
KW - Breast cancer
KW - Kenya
KW - Molecular subtypes
KW - Risk factors
KW - Sub-Saharan Africa
UR - http://www.scopus.com/inward/record.url?scp=85109644328&partnerID=8YFLogxK
U2 - 10.1186/s13058-021-01446-3
DO - 10.1186/s13058-021-01446-3
M3 - Article
C2 - 34174935
AN - SCOPUS:85109644328
SN - 1465-5411
VL - 23
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 68
ER -
