Why Breast Cancer is Higher in Black Women

In 1994 I first suggested that testosterone may be involved in causing breast cancer (International Journal of Cancer 2005; 115: 497 and Annals of Internal Medicine 2005; 142: 471-472). For example, smoking increases breast cancer risk (Cancer Causes Control. 2005 Oct;16(8):975-85) and smoking in premenopausal women increases testosterone (Eur J Epidemiol. 2005;20(4):331-7). Alcohol “is associated with increased breast cancer risk” (Alcohol. 2005 Apr;35(3):213-25) and alcohol increases testosterone levels in premenopausal women (J Clin Endocrinol Metab. 2001 May;86(5):1981-5). “Abdominal fat has been shown to be an important risk factor for …breast cancer.” in premenopausal women (Genet Epidemiol. 2001 May;20(4):458-78) and higher free testosterone has been connected with abdominal fat accumulation (Wien Klin Wochenschr. 2002 May 15;114(8-9):321-6). Again, I suggest testosterone is involved in breast cancer. The mechanism involves the effect of reduced DHEA on certain genes, as a consequence of reduced conversion of DHEAS to DHEA caused by testosterone. (Hormone replacement therapy (HRT) also reduces DHEA and may be why HRT increases breast cancer.) However, to satisfy the intention of this treatise, I will deal only with testosterone.

While controversial, that is, there is not absolute agreement, most studies find higher levels of testosterone in African-American women compared to European-Americans (black and white). Testosterone was recently reported to be higher in African-American women compared to Caucasian women (Cancer Epidemiol Biomarkers Prev. 2005 Jun;14(6):1514-20). I suggest this increased testosterone affects the epidemiology of breast cancer within these two populations.

“African American women have a lower overall incidence of breast cancer but a higher overall mortality than do white women. African American women with breast cancer present for medical care at an earlier age, with more advanced stage disease, and with higher-risk tumor biology. While the advanced stage at presentation and higher-risk tumor biology appear to account for much of the excess mortality in African American women, differences persist even after controlling for these factors. This paper discusses the factors that may contribute to differences in survival and differences in stage at diagnosis between African American and white women.” (Perspect Biol Med. 2005 Winter;48(1 Suppl):S166-75)

As a biologist, I suggest some diseases produce differential reproduction in some groups by reducing representation within current populations. Breast cancer may cause this phenomenon in black women. If black women are more prone to breast cancer, it is possible that vulnerable black women were adversely affected in the past before comprehensive epidemiological studies could have found them. That is, there may have been a time when black women exhibited more breast cancer incidence than white women. This may have reduced the percentage of vulnerable black women at that time. However, when those who are currently vulnerable develop breast cancer, the increased testosterone may produce much earlier, more pronounced cancers. The quotation, above, does report earlier age and more aggressive tumors in black women who develop breast cancer at this time. I suggest this supports my interpretation that the population of black women of today may have been preceded by a population of black women in the past who developed breast cancer early in their lives and are reduced in the current population. I suggest this may be seen in the following quotation.

“RESULTS: Women from sub-Saharan Africa were found to have a low incidence of breast cancer. This was partly explained by a largely protective reproductive history, including late menarche, early menopause, high parity with prolonged breastfeeding, irregular menses, and fewer ovulatory cycles. The average age at diagnosis, however, was approximately 10 years younger than breast cancer patients of western nations, and disease stage distribution was shifted toward more advanced disease, which resulted in higher mortality rates. These features were found to be similar to data on breast cancer in African-American women. Mutations in BRCA1 and BRCA2 have been reported in African-American women, but the extent of the contribution of BRCA1 and BRCA2 to breast cancer burden in Africa was uncertain. Limited financial resources lead to suboptimal cancer data collection, as well as delayed diagnosis and treatment of many African breast cancer patients.” (Cancer. 2005 Apr 15;103(8):1540-50)

It is my hypothesis that the "secular trend," the increase in size and earlier puberty of children, is caused by an increase in the percentage of individuals of higher testosterone within populations. This is driven by increases in the percentage of women of higher testosterone. (Some say the trend is due to increased calories; increased calories only increases reproduction of this percentage of the population, not cause it.) It is this increase in percentage of women of higher testosterone that may be the cause of the increase in breast cancer …if increased testosterone is part of the causative mechanism. If I am correct, at some time in the future epidemiology will find a reduction of breast cancer in white women along with an increase in earlier age at onset with more aggressive tumors.

New Supporting Research:

J Clin Oncol. 2006 Mar 20;24(9):1342-9.

Meta-analysis of survival in African American and white American patients with breast cancer: ethnicity compared with socioeconomic status.

Newman LA, Griffith KA, Jatoi I, Simon MS, Crowe JP, Colditz GA.

University of Michigan, Ann Arbor, MI 48109, USA

PURPOSE: The extent to which socioeconomic disadvantages and inadequate health care access account for the disproportionately elevated mortality hazard observed in African American compared with white American patients with breast cancer is poorly defined. METHODS: We identified 20 studies reported between January 1980 and June 2005 that provided survival analyses in patients with breast cancer after adjusting for ethnicity and some measurement of socioeconomic status. These studies also adjusted for age and stage of disease at time of diagnosis. RESULTS: The pooled outcome data yielded estimates for the mortality hazard in 14,013 African American and 76,111 white American patients with breast cancer. Studies varied in their methods for assigning socioeconomic status, with most relying on area-wide measures such as census tract and census block data. The combined analysis (adjusted for age, stage, and socioeconomic status) revealed that African American ethnicity was associated with a statistically significant excess mortality risk in overall survival (mortality hazard, 1.27; 95% CI, 1.18 to 1.38) and in breast cancer-specific survival (mortality hazard, 1.19; 95% CI, 1.10 to 1.29). CONCLUSION: Our pooled analysis demonstrated that African American ethnicity is a significant and independent predictor of poor outcome from breast cancer, even after accounting for socioeconomic status by conventional measures. These findings support the need for further investigation of the biologic, genetic, and sociocultural factors that may influence survival in African American patients with breast cancer.

JAMA. 2006 Jun 7;295(21):2492-502.

Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study.

Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC.

Division of Hematology/Oncology, School of Public Health, Department of Epidemiology, University of North Carolina-Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599-7305, USA.

CONTEXT: Gene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER-), luminal A, and luminal B. OBJECTIVES: To determine population-based distributions and clinical associations for breast cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS: Immunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified (negative for all 5 markers). MAIN OUTCOME MEASURES: We examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER- subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer-specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER- and basal-like subtypes. CONCLUSIONS: Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non-African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.