Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort
Qingqing Hu, Chun-Pin Esther Chang, John Snyder
Vikrant Deshmukh, Porucznik C , David K. Gaffney, Chun-Pin Chang, Alison Fraser, Lisa H Gren, Mia Hashibe, N Lynn Henry, Ivette Lopez, Michael Newman, Christina A Porucznik, Kerry Rowe, Ken R Smith, Joseph B Stanford
Author affiliations (7)
Division of Public Health, Department of Family & Preventive Medicine, University of Utah School of Medicine.ROR
Department of Family and Preventive Medicine, Office of Cooperative Reproductive Health, Division of Public Health, Spencer Fox Eccles School of Medicine, University of Utah, Salt Lake City, United...
Division of Public Health, Department of Family and Preventive Medicine, University of Utah School of Medicine, and Huntsman Cancer Institute, Salt Lake City, UT, United States of America.
Breast cancer is the leading cause of cancer death among Hispanic women. The aim of our study was to estimate cardiovascular disease (CVD) risk among Hispanic and non-Hispanic White (NHW) breast cancer survivors compared with their respective general population cohorts.
Methods
Cohorts of 17 469 breast cancer survivors (1774 Hispanic and 15 695 NHW) in the Utah Cancer Registry diagnosed between 1997 and 2016, and 65 866 women (6209 Hispanic and 59 657 NHW) from the general population in the Utah Population Database were identified. Cox proportional hazards models were used to estimate hazard ratios (HRs) for CVD.
Results
The risk of diseases of the circulatory system was higher in Hispanic than NHW breast cancer survivors 1-5 years after cancer diagnosis, in comparison with their respective general population cohorts (HR(Hispanic) = 1.94, 99% confidence interval [CI] = 1.49 to 2.53; H(NHW) = 1.38, 99% CI = 1.33 to 1.43; 2-sided P (heterogeneity) = .01, respectively). Increased risks were observed for both Hispanic and NHW breast cancer survivors for diseases of the heart and the veins and lymphatics, compared with the general population cohorts. More than 5 years after cancer diagnosis, elevated risk of diseases of the veins and lymphatics persisted in both ethnicities. The CVD risk due to chemotherapy and hormone therapy was higher in Hispanic than NHW breast cancer survivors but did not differ for distant stage, higher baseline comorbidities, or baseline smoking.
Conclusions
We observed a risk difference for diseases of the circulatory system between Hispanic and NHW breast cancer survivors compared with their respective general population cohorts but only within the first 5 years of cancer diagnosis.
cardiovascular disease Hispanic breast cancer, CVD risk breast cancer survivors, health disparities Hispanic women, cancer survivorship cardiovascular, breast cancer treatment cardiac effects, population-based cohort cancer CVD, ethnic disparities cancer outcomes, Hispanic women cardiovascular risk factors, cancer survivor long-term health, breast cancer cardiovascular comorbidity
PMID 33889806 33889806 DOI 10.1093/jncics/pkab016 10.1093/jncics/pkab016 Hu et al. 2021, Hu 2021
Cite this article
Hu, Q., Chang, C. P., Rowe, K., Snyder, J., Deshmukh, V., Newman, M., Fraser, A., Smith, K., Gren, L. H., Porucznik, C., Stanford, J. B., Gaffney, D., Henry, N. L., Lopez, I., & Hashibe, M. (2021). Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort. JNCI cancer spectrum, 5(2). https://doi.org/10.1093/jncics/pkab016
Hu Q, Chang CP, Rowe K, Snyder J, Deshmukh V, Newman M, et al. Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort. JNCI Cancer Spectr. 2021;5(2). doi:10.1093/jncics/pkab016
Hu, Q., et al. "Disparities in Cardiovascular Disease Risk Among Hispanic Breast Cancer Survivors in a Population-Based Cohort." JNCI cancer spectrum, vol. 5, no. 2, 2021.
Giaquinto AN et al., 2024·CA: A Cancer Journal for Clinicians·
Open Access
This is the American Cancer Society's biennial update of statistics on breast cancer among women based on high-quality incidence and mortality data from the National Cancer Institute and the Centers for Disease Control and Prevention. Breast cancer incidence continued an upward trend, rising by 1% annually during 2012-2021, largely confined to localized-stage and hormone receptor-positive disease. A steeper increase in women younger than 50 years (1.4% annually) versus 50 years and older (0.7%) overall was only significant among White women. Asian American/Pacific Islander women had the fastest increase in both age groups (2.7% and 2.5% per year, respectively); consequently, young Asian American/Pacific Islander women had the second lowest rate in 2000 (57.4 per 100,000) but the highest rate in 2021 (86.3 per 100,000) alongside White women (86.4 per 100,000), surpassing Black women (81.5 per 100,000). In contrast, the overall breast cancer death rate continuously declined during 1989-2022 by 44% overall, translating to 517,900 fewer breast cancer deaths during this time. However, not all women have experienced this progress; mortality remained unchanged since 1990 in American Indian/Alaska Native women, and Black women have 38% higher mortality than White women despite 5% lower incidence. Although the Black-White disparity partly reflects more triple-negative cancers, Black women have the lowest survival for every breast cancer subtype and stage except localized disease, with which they are 10% less likely to be diagnosed than White women (58% vs. 68%), highlighting disadvantages in social determinants of health. Progress against breast cancer could be accelerated by mitigating racial, ethnic, and social disparities through improved clinical trial representation and access to high-quality screening and treatment.
A recent Perspective article asserted that progesterone secretion during ovulatory cycles is the cause of breast cancer. However, we challenge most of the evidence developed in this publication. First, there is a lack of evidence that progesterone is mutagenic for breast cells. Cause of a cancer should mean initiation by mutation, as opposed to promotion. Second, subclinical ovulatory disturbances occur rather frequently in normal-length menstrual cycles. Third, the authors attribute a potential carcinogenic effect to progesterone secreted during menstrual cycles but not to progesterone during pregnancy. They did not discuss breast cancer evidence from progesterone/progestin therapeutics. They argue that in genetic primary amenorrhea, a hypothetic lower risk of breast cancer could be due to the lack of progesterone, despite the progesterone/progestin in hormone replacements these women receive. Fourth, they advocate a regulatory effect of progesterone on several genes potentially involved in cancer genesis. In particular, they attribute a lower risk of breast cancer in women with Mayer-Rokitansky-Küster-Hauser syndrome to a defect in the progesterone-stimulated Wnt4 gene. However, this defect is only present in a small subset. Thus, the postulated progesterone breast cancer risk is unconvincing, which we discuss point by point in this commentary.
Maurya AP et al., 2023·Indian J Cancer·
Open Access
The incidence of breast cancer in India has seen a rapid increase in recent years. Hormonal and reproductive risk factors for breast cancer have been affected by socioeconomic development. Studies on breast cancer risk factors in India are limited by the small sample size and specific geographical area. The current systematic review was carried out to assess the association of hormonal and reproductive risk factors with breast cancer in Indian women. A systematic review of MEDLINE, Embase, Scopus, and Cochrane database of systematic reviews were done. Relevant case-control studies published in peer-reviewed indexed journals were analyzed for hormonal risk factors such as age at menarche, menopause, and first childbirth; breastfeeding; abortion; and oral contraceptive pills use. Younger age (<13 years) at menarche was associated with high risk (odds ratio 1.23-3.72). Other hormonal risk factors with strong association were age at first childbirth and menopause, parity, and duration of breastfeeding. Abortion and the use of contraceptive pills did not have a clear association with breast cancer. Hormonal risk factors have a higher association in premenopausal disease and estrogen receptor-positive tumors. There is a strong association between hormonal and reproductive risk factors and breast cancer in Indian women. The protective effect of breastfeeding is related to the cumulative duration of breastfeeding.
Current or recent use of combined oral contraceptives (containing oestrogen+progestagen) has been associated with a small increase in breast cancer risk. Progestagen-only contraceptive use is increasing, but information on associated risks is limited. We aimed to assess breast cancer risk associated with current or recent use of different types of hormonal contraceptives in premenopausal women, with particular emphasis on progestagen-only preparations. Hormonal contraceptive prescriptions recorded prospectively in a UK primary care database (Clinical Practice Research Datalink [CPRD]) were compared in a nested case-control study for 9,498 women aged <50 years with incident invasive breast cancer diagnosed in 1996 to 2017, and for 18,171 closely matched controls. On average, 7.3 (standard deviation [SD] 4.6) years of clinical records were available for each case and their matched controls prior to the date of diagnosis. Conditional logistic regression yielded odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer by the hormonal contraceptive type last prescribed, controlled for age, GP practice, body mass index, number of recorded births, time since last birth, and alcohol intake. MEDLINE and Embase were searched for observational studies published between 01 January 1995 and 01 November 2022 that reported on the association between current or recent progestagen-only contraceptive use and breast cancer risk in premenopausal women. Fixed effects meta-analyses combined the CPRD results with previously published results from 12 observational studies for progestagen-only preparations. Overall, 44% (4,195/9,498) of women with breast cancer and 39% (7,092/18,171) of matched controls had a hormonal contraceptive prescription an average of 3.1 (SD 3.7) years before breast cancer diagnosis (or equivalent date for controls). About half the prescriptions were for progestagen-only preparations. Breast cancer ORs were similarly and significantly raised if the last hormonal contraceptive prescription was for oral combined, oral progestagen-only, injected progestagen, or progestagen-releasing intrauterine devices (IUDs): ORs = 1.23 (95% CI [1.14 to 1.32]; p < 0.001), 1.26 (95% CI [1.16 to 1.37]; p < 0.001), 1.25 (95% CI [1.07 to 1.45]; p = 0.004), and 1.32 (95% CI [1.17 to 1.49]; p < 0.001), respectively. Our meta-analyses yielded significantly raised relative risks (RRs) for current or recent use of progestagen-only contraceptives: oral = 1.29 (95% CI [1.21 to 1.37]; heterogeneity χ25 = 6.7; p = 0.2), injected = 1.18 (95% CI [1.07 to 1.30]; heterogeneity χ28 = 22.5; p = 0.004), implanted = 1.28 (95% CI [1.08 to 1.51]; heterogeneity χ23 = 7.3; p = 0.06), and IUDs = 1.21 (95% CI [1.14 to 1.28]; heterogeneity χ24 = 7.9; p = 0.1). When the CPRD results were combined with those from previous published findings (which included women from a wider age range), the resulting 15-year absolute excess risk associated with 5 years use of oral combined or progestagen-only contraceptives in high-income countries was estimated at: 8 per 100,000 users from age 16 to 20 years and 265 per 100,000 users from age 35 to 39 years. The main limitation of the study design was that, due to the nature of the CPRD data and most other prescription databases, information on contraceptive use was recorded during a defined period only, with information before entry into the database generally being unavailable. This means that although our findings provide evidence about the short-term associations between hormonal contraceptives and breast cancer risk, they do not provide information regarding longer-term associations, or the impact of total duration of contraceptive use on breast cancer risk. This study provides important new evidence that current or recent use of progestagen-only contraceptives is associated with a slight increase in breast cancer risk, which does not appear to vary by mode of delivery, and is similar in magnitude to that associated with combined hormonal contraceptives. Given that the underlying risk of breast cancer increases with advancing age, the absolute excess risk associated with use of either type of oral contraceptive is estimated to be smaller in women who use it at younger rather than at older ages. Such risks need be balanced against the benefits of using contraceptives during the childbearing years.