Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

Chlebowski, Rowan T.; Manson, JoAnn E.; Anderson, Garnet L.; Cauley, Jane A.; Aragaki, Aaron K.; Stefanick, Marcia L.; Lane, Dorothy S.; Johnson, Karen C.; Wactawski‐Wende, Jean; Chen, Chu; Qi, Lihong; Yasmeen, Shagufta; Newcomb, Polly A.; Prentice, Ross L.

doi:10.1093/jnci/djt043

Cited by 172 publications

(141 citation statements)

References 37 publications

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“…Although it is likely that HRT is a risk factor for breast cancer in Asian women, as in women from other countries (Fournier et al, 2005;Chlebowski et al, 2013), in countries that have limited resources and research funding, ecologic and cross-sectional studies may assist with risk stratification (Hoel et al, 1983;Koo et al, 1997;Zhang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors

Kim¹,

Yoo

Goodman

2015

Asian Pacific Journal of Cancer Prevention

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Section: Discussionmentioning

confidence: 99%

Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors

Kim¹,

Yoo

Goodman

2015

Asian Pacific Journal of Cancer Prevention

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“…Breast cancer risk factors include weight gain after age 18 years, excess body weight (for postmenopausal breast cancer), use of menopausal hormone therapy (MHT), physical inactivity, alcohol consumption, and reproductive and hormonal factors, such as a long menstrual history, recent use of oral contraceptives, and nulliparity or later age at first birth (29,30). Breastfeeding decreases the risk of breast cancer (30).…”

Section: Female Breastmentioning

confidence: 99%

Global Cancer Incidence and Mortality Rates and Trends—An Update

Torre

Siegel

Ward

et al. 2016

Cancer Epidemiology, Biomarkers &Amp; Prevention

2,997

2,186

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There are limited published data on recent cancer incidence and mortality trends worldwide. We used the International Agency for Research on Cancer's CANCERMondial clearinghouse to present age-standardized cancer incidence and death rates for [2003][2004][2005][2006][2007]. We also present trends in incidence through 2007 and mortality through 2012 for select countries from five continents. High-income countries (HIC) continue to have the highest incidence rates for all sites, as well as for lung, colorectal, breast, and prostate cancer, although some low-and middle-income countries (LMIC) now count among those with the highest rates. Mortality rates from these cancers are declining in many HICs while they are increasing in LMICs. LMICs have the highest rates of stomach, liver, esophageal, and cervical cancer. Although rates remain high in HICs, they are plateauing or decreasing for the most common cancers due to decreases in known risk factors, screening and early detection, and improved treatment (mortality only). In contrast, rates in several LMICs are increasing for these cancers due to increases in smoking, excess body weight, and physical inactivity. LMICs also have a disproportionate burden of infection-related cancers. Applied cancer control measures are needed to reduce rates in HICs and arrest the growing burden in LMICs.Cancer Epidemiol Biomarkers Prev; 25(1); 16-27. Ó2015 AACR.

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“…26,27 However, estrogen is not a risk for BC for all women, as has become clear through clinical studies of HRT use. 28,29 Initially, the Million Women Study and Women's Health Initiative reported that current and/or prolonged use of HRT correlated with an increased risk of BC. Because these tumors tended to be lower grade, with over-representation of lobular or tubular subtypes compared to other ductal cancers, 30 it was hypothesized that HRT was causing cancers that otherwise would not have arisen.…”

Section: Introductionmentioning

confidence: 99%

Estrogen withdrawal, increased breast cancer risk and the KRAS-variant

et al. 2015

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Keywords: breast cancer risk, estrogen withdrawal, KRAS-variant, multiple primary breast cancer, triple negative breast cancer, tumor biologyThe KRAS-variant is a biologically functional, microRNA binding site variant, which predicts increased cancer risk especially for women. Because external exposures, such as chemotherapy, differentially impact the effect of this mutation, we evaluated the association of estrogen exposures, breast cancer (BC) risk and tumor biology in women with the KRAS-variant. Women with BC (n D 1712), the subset with the KRAS-variant (n D 286) and KRAS-variant unaffected controls (n D 80) were evaluated, and hormonal exposures, KRAS-variant status, and pathology were compared. The impact of estrogen withdrawal on transformation of isogenic normal breast cell lines with or without the KRAS-variant was studied. Finally, the association and presentation characteristics of the KRAS-variant and multiple primary breast cancer (MPBC) were evaluated. KRAS-variant BC patients were more likely to have ovarian removal pre-BC diagnosis than non-variant BC patients (p D 0.033). In addition, KRAS-variant BC patients also appeared to have a lower estrogen state than KRAS-variant unaffected controls, with a lower BMI (P < 0.001). Finally, hormone replacement therapy (HRT) discontinuation in KRAS-variant patients was associated with a diagnosis of triple negative BC (P < 0.001). Biologically confirming our clinical findings, acute estrogen withdrawal led to oncogenic transformation in KRAS-variant positive isogenic cell lines. Finally, KRAS-variant BC patients had greater than an 11-fold increased risk of presenting with MPBC compared to non-variant patients (45.39% vs 6.78%,.87], P < 0.001). Thus, estrogen withdrawal and a low estrogen state appear to increase BC risk and to predict aggressive tumor biology in women with the KRAS-variant, who are also significantly more likely to present with multiple primary breast cancer.

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Estrogen Plus Progestin and Breast Cancer Incidence and Mortality in the Women’s Health Initiative Observational Study

Abstract: Consistent with WHI randomized trial findings, estrogen plus progestin use is associated with increased breast cancer incidence. Because prognosis after diagnosis on combined hormone therapy is similar to that of nonusers, increased breast cancer mortality can be expected.

Cited by 172 publications

References 37 publications

Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors

Differences in Incidence, Mortality and Survival of Breast Cancer by Regions and Countries in Asia and Contributing Factors

Global Cancer Incidence and Mortality Rates and Trends—An Update

Estrogen withdrawal, increased breast cancer risk and the KRAS-variant

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