Abstract
An increased risk of breast cancer has been reported in patients with non-melanomatous skin cancer (NMSC), but this association has not been studied in a large, multi-geographic population. We utilized data from the Women’s Health Initiative observational study to assess whether history of NMSC is associated with breast cancer risk. This analysis included 70,246 postmenopausal White and Hispanic women aged 50–79, in which 4,247 breast cancer cases were identified over a mean (SD) of 11.3 (3.2) years. Baseline information was collected on demographics, medical history, sun exposure, and vitamin D intake. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs). The relationship between NMSC and breast cancer was examined as a time-dependent exposure using updated information on NMSC gathered during follow-up visits. All statistical tests were two sided. There were 5,595 women diagnosed with NMSC at study entry. The annualized rate of breast cancer was 0.64 % among women with a history of NMSC and 0.55 % among women with no history of NMSC. The multivariable-adjusted HR for breast cancer among women with a history of NMSC versus no history of NMSC was 1.07 (95 % CI 0.95–1.20, P = 0.27). Further evaluation stratified by tumor characteristics showed an increased risk of lymph node-positive disease, HR = 1.30 (95 % CI 1.01–1.67, P = 0.04), and regional-stage disease, HR = 1.33 (95 % CI 1.05–1.70, P = 0.02), among women with NMSC. There was no significant overall association between NMSC and breast cancer; however, there was an increased risk of more advanced-stage breast cancer which needs further exploration.
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References
American Cancer Society (2012) Cancer Facts & Figures 2012. American Cancer Society, Atlanta
Frank TS, Critchfield GC (2002) Hereditary risk of women’s cancers. Best Pract Res Clin Obstet Gynaecol 16:703–713
Rosenberg CA, Greenland P, Khandekar J, Loar A, Ascensao J, Lopez AM (2004) Association of nonmelanoma skin cancer with second malignancy. Cancer 100:130–138
Cantwell MM, Murray LJ, Catney D, Donnelly D, Autier P, Boniol M, Fox C, Middleton RJ, Dolan OM, Gavin AT (2009) Second primary cancers in patients with skin cancer: a population-based study in Northern Ireland. Br J Cancer 100:174–177
Frisch M, Melbye M (1995) New primary cancers after squamous cell skin cancer. Am J Epidemiol 141:916–922
Frisch M, Hjalgrim H, Olsen JH, Melbye M (1996) Risk for subsequent cancer after diagnosis of basal-cell carcinoma. A population-based, epidemiologic study. Ann Intern Med 125:815–821
Hemminki K, Dong C (2000) Subsequent cancers after in situ and invasive squamous cell carcinoma of the skin. Arch Dermatol 136:647–651
Lindelof B, Sigurgeirsson B, Wallberg P, Eklund G (1991) Occurrence of other malignancies in 1973 patients with basal cell carcinoma. J Am Acad Dermatol 25:245–248
Maitra SK, Gallo H, Rowland-Payne C, Robinson D, Moller H (2005) Second primary cancers in patients with squamous cell carcinoma of the skin. Br J Cancer 92:570–571
Milan T, Pukkala E, Verkasalo PK, Kaprio J, Jansen CT, Koskenvuo M, Teppo L (2000) Subsequent primary cancers after basal-cell carcinoma: a nationwide study in Finland from 1953 to 1995. Int J Cancer 87:283–288
Nugent Z, Demers AA, Wiseman MC, Mihalcioiu C, Kliewer EV (2005) Risk of second primary cancer and death following a diagnosis of nonmelanoma skin cancer. Cancer Epidemiol Biomarkers Prev 14:2584–2590
Chen J, Ruczinski I, Jorgensen TJ, Yenokyan G, Yao Y, Alani R, Liegeois NJ, Hoffman SC, Hoffman-Bolton J, Strickland PT, Helzlsouer KJ, Alberg AJ (2008) Nonmelanoma skin cancer and risk for subsequent malignancy. J Natl Cancer Inst 100:1215–1222
Efird JT, Friedman GD, Habel L, Tekawa IS, Nelson LM (2002) Risk of subsequent cancer following invasive or in situ squamous cell skin cancer. Ann Epidemiol 12:469–475
Friedman GD, Tekawa IS (2000) Association of basal cell skin cancers with other cancers (United States). Cancer Causes Control 11:891–897
Levi F, Randimbison L, Te VC, Conconi MM, La VC (2008) Risk of prostate, breast and colorectal cancer after skin cancer diagnosis. Int J Cancer 123:2899–2901
Krueger H, Williams D (2010) Burden of malignancy after a primary skin cancer: recurrence, multiple skin cancers and second primary cancers. Can J Public Health 101:I23–I27
Hemminki K, Li X (2002) Cancer risks in Nordic immigrants and their offspring in Sweden. Eur J Cancer 38:2428–2434
Ginsburg OM, Kim-Sing C, Foulkes WD, Ghadirian P, Lynch HT, Sun P, Narod SA (2010) BRCA1 and BRCA2 families and the risk of skin cancer. Fam Cancer 9:489–493
Hussein MR (2005) Ultraviolet radiation and skin cancer: molecular mechanisms. J Cutan Pathol 32:191–205
Robsahm TE, Tretli S, Dahlback A, Moan J (2004) Vitamin D3 from sunlight may improve the prognosis of breast-, colon- and prostate cancer (Norway). Cancer Causes Control 15:149–158
Millen AE, Pettinger M, Freudenheim JL, Langer RD, Rosenberg CA, Mossavar-Rahmani Y, Duffy CM, Lane DS, McTiernan A, Kuller LH, Lopez AM, Wactawski-Wende J (2009) Incident invasive breast cancer, geographic location of residence, and reported average time spent outside. Cancer Epidemiol Biomarkers Prev 18:495–507
Garland CF, Garland FC, Gorham ED (1999) Calcium and vitamin D. Their potential roles in colon and breast cancer prevention. Ann N Y Acad Sci 889:107–119
Garland CF, Gorham ED, Mohr SB, Grant WB, Giovannucci EL, Lipkin M, Newmark H, Holick MF, Garland FC (2007) Vitamin D and prevention of breast cancer: pooled analysis. J Steroid Biochem Mol Biol 103:708–711
Garland FC, Garland CF, Gorham ED, Young JF (1990) Geographic variation in breast cancer mortality in the United States: a hypothesis involving exposure to solar radiation. Prev Med 19:614–622
Freedman DM, Dosemeci M, McGlynn K (2002) Sunlight and mortality from breast, ovarian, colon, prostate, and non-melanoma skin cancer: a composite death certificate based case-control study. Occup Environ Med 59:257–262
Tuohimaa P, Pukkala E, Scelo G, Olsen JH, Brewster DH, Hemminki K, Tracey E, Weiderpass E, Kliewer EV, Pompe-Kirn V, McBride ML, Martos C, Chia KS, Tonita JM, Jonasson JG, Boffetta P, Brennan P (2007) Does solar exposure, as indicated by the non-melanoma skin cancers, protect from solid cancers: vitamin D as a possible explanation. Eur J Cancer 43:1701–1712
Wheless L, Black J, Alberg AJ (2010) Nonmelanoma skin cancer and the risk of second primary cancers: a systematic review. Cancer Epidemiol Biomarkers Prev 19:1686–1695
Patterson RE, Kristal AR, Tinker LF, Carter RA, Bolton MP, Agurs-Collins T (1999) Measurement characteristics of the Women’s Health Initiative food frequency questionnaire. Ann Epidemiol 9:178–187
The Women’s Health Initiative Study Group (1998) Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials 19:61–109
Langer RD, White E, Lewis CE, Kotchen JM, Hendrix SL, Trevisan M (2003) The Women’s Health Initiative observational study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol 13:S107–S121
Anderson GL, Manson J, Wallace R, Lund B, Hall D, Davis S, Shumaker S, Wang CY, Stein E, Prentice RL (2003) Implementation of the Women’s Health Initiative study design. Ann Epidemiol 13:S5–S17
el KF, Bedwani R, D’Avanzo B, Assaad S, el Shafei AA, Mokhtar S, La VC (1994) Risk factors for non-melanomatous skin cancer in Alexandria, Egypt. Int J Cancer 56:375–378
Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ (1989) Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81:1879–1886
Irwin ML, McTiernan A, Manson JE, Thomson CA, Sternfeld B, Stefanick ML, Wactawski-Wende J, Craft L, Lane D, Martin LW, Chlebowski R (2011) Physical activity and survival in postmenopausal women with breast cancer: results from the women’s health initiative. Cancer Prev Res (Phila) 4:522–529
Song F, Qureshi AA, Giovannucci EL, Fuchs CS, Chen WY, Stampfer MJ, Han J (2013) Risk of a second primary cancer after non-melanoma skin cancer in white men and women: a prospective cohort study. PLoS Med 10:e1001433
Levi F, Randimbison L, La VC, Erler G, Te VC (1997) Incidence of invasive cancers following squamous cell skin cancer. Am J Epidemiol 146:734–739
Askling J, Sorensen P, Ekbom A, Frisch M, Melbye M, Glimelius B, Hjalgrim H (1999) Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer? Ann Intern Med 131:655–659
Dybbro E, Mihalis E, Hirose R, Arron ST (2012) Validity of patient skin cancer report among organ transplant recipients. Clin Transplant 26:E132–E136
Millen AE, Wactawski-Wende J, Pettinger M, Melamed ML, Tylavsky FA, Liu S, Robbins J, LaCroix AZ, LeBoff MS, Jackson RD (2010) Predictors of serum 25-hydroxyvitamin D concentrations among postmenopausal women: the Women’s Health Initiative calcium plus vitamin D clinical trial. Am J Clin Nutr 91:1324–1335
Acknowledgments
We acknowledge the dedicated efforts of investigators and staff at the Women’s Health Initiative (WHI) clinical centers, the WHI Clinical Coordinating Center, and the National Heart, Lung, and Blood program office (listing available at http://www.whi.org). We also recognize the WHI participants for their extraordinary commitment to the WHI program. For a list of all the investigators who have contributed to the WHI science, please visit http://www.whiscience.org/publications/WHI_investigators_longlist.pdf. The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts N01WH22110, 24152, 32100-2, 32105-6, 32108-9, 32111-13, 32115, 32118-32119, 32122, 42107-26, 42129-32, and 44221, and the Cancer Center Support Grant NIH: NCI P30CA022453.
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There are no conflicts of interest or financial relationships with the organization that sponsored the research.
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Pressler, M., Rosenberg, C.A., Derman, B.A. et al. Breast cancer in postmenopausal women after non-melanomatous skin cancer: the Women’s Health Initiative observational study. Breast Cancer Res Treat 139, 821–831 (2013). https://doi.org/10.1007/s10549-013-2578-y
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DOI: https://doi.org/10.1007/s10549-013-2578-y