Gynaecological malignancies after breast cancer diagnosis: A population-based study
Main Article Content
Abstract
Background: Breast cancer (BC) is one of the most prevalent malignancies. BC survivors have higher risk of second primary cancers than the general population. There is an increased interest in BC survivor management, including the prevention of these second cancers. The aim of this study was to assess the risk of gynaecological malignancy (GM) as second neoplasm among BC patients in our population.
Methods: Patients with invasive BC diagnosed from 1980 to 2014 included in the Girona Cancer Registry were included. The incidence of second GM in these patients was compared to those in the general population. Second primary cancer was stated as a tumour diagnosed after 2 months from the BC diagnosis. Standardized incidence ratios (SIR) and absolute excess of risk (AER) were calculated.
Results: 9,717 patients were diagnosed with invasive BC during this period, with a median age at diagnosis of 61 years, and a median follow-up of 7.9 years. 117 of them developed a second GM. By tumour type, the only statistically significant higher SIR was observed for corpus uteri cancer (SIR:2.28 95% CI 1.82-2.83; AER:6.43 95% CI 4.13-9.14). After reviewing the histology of the corpus uteri cancer cases, we found that 71.4% were type I (endometrioid adenocarcinoma), 15.5% type II (serous adenocarcinomas and clear cell carcinomas), 10.7% carcinosarcomas, 2.4% sarcomas and there were no unspecified malignant neoplasms.
Conclusion: BC survivors have an increased risk of corpus uteri cancer, with an increase in unfavourable histologies compared to the general population. Lifelong primary and secondary prevention interventions should be recommended for these patients.
Article Details
Copyright (c) 2019 Barretina-Ginesta MP, et al.

This work is licensed under a Creative Commons Attribution 4.0 International License.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, et al. Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2018; 68: 394–424. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30207593
Clèries R, Ameijide A, Marcos-Gragera R, Pareja L, Carulla M, et al. Predicting the cancer burden in Catalonia between 2015 and 2025: the challenge of cancer management in the elderly. Clin Transl Oncol. 2018; 20: 647–657. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29027110
Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet (London, England). 2018; 391: 1023–1075. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29395269
Pollán M, Pastor-Barriuso R, Ardanaz E, Argüelles M, Martos C, et al. Recent changes in breast cancer incidence in Spain, 1980-2004. J Natl Cancer Inst. 2009; 101: 1584–1591. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19861303
Matesich SMA, Shapiro CL. Second cancers after breast cancer treatment. Semin Oncol. 2003; 30: 740–748. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/14663775
Liu J, Jiang W, Mao K, An Y, Su F, et al. Elevated risks of subsequent endometrial cancer development among breast cancer survivors with different hormone receptor status: a SEER analysis. Breast Cancer Res Treat. 2015; 150: 439–445. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25764167
Demark-Wahnefried W, Aziz NM, Rowland JH, Pinto BM. Riding the crest of the teachable moment: Promoting long-term health after the diagnosis of cancer. J Clin Oncol. 2005; 23: 5814–5830. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16043830
Suris-Swartz PJ, Schildkraut JM, Vine MF, Hertz-Picciotto I. Age at diagnosis and multiple primary cancers of the breast and ovary. Breast Cancer Res Treat. 1996; 41: 21–29. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8932873
Stratton JF, Gayther SA, Russell P, Dearden J, Gore M, et al. Contribution of BRCA1 mutations to ovarian cancer. N Engl J Med. 1997; 336: 1125–1130. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9099656
Nagy E, Gajjar KB, Patel II, Taylor S, Martin-Hirsch PL, et al. MGMT promoter hypermethylation and K-RAS, PTEN and TP53 mutations in tamoxifen-exposed and non-exposed endometrial cancer cases. Br J Cancer. 2014; 110: 2874–2880. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24853176
Mellemkjær L, Friis S, Olsen JH, Scélo G, Hemminki K, et al. Risk of second cancer among women with breast cancer. Int J Cancer. 2006; 118: 2285–2292. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16342146
Volk N, Pompe-Kirn V. Second primary cancers in breast cancer patients in Slovenia. Cancer Causes Control. 1997; 8: 764–770. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9328199
Harvey EB, Brinton LA. Second cancer following cancer of the breast in Connecticut, 1935-82. Natl Cancer Inst Monogr. 1985; 68: 99–112. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/4088315
Soerjomataram I, Louwman WJ, De Vries E, Lemmens VEPP, Klokman WJ, et al. Primary malignancy after primary female breast cancer in the south of the Netherlands, 1972-2001. Breast Cancer Res Treat. 2005; 93: 91–95. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16184464
Gulhan I, Eser S, Yakut C, Bige O, Ilhan E, et al. Second primary gynecologic cancers after breast cancer in Turkish women. Int J Gynecol Cancer. 2009; 19: 648–650. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19509564
Molina-Montes E, Pollán M, Payer T, Molina E, Dávila-Arias C, et al. Risk of second primary cancer among women with breast cancer: A population-based study in Granada (Spain). Gynecol Oncol. 2013; 130: 340–345. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23648471
Jones ME, van Leeuwen FE, Hoogendoorn WE, Mourits MJE, Hollema H, et al. Endometrial cancer survival after breast cancer in relation to tamoxifen treatment: Pooled results from three countries. Breast Cancer Res. 2012; 14: R91. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22691381
Hall HI, Jamison P, Weir HK. Second primary ovarian cancer among women diagnosed previously with cancer. Cancer Epidemiol Biomarkers Prev. 2001; 10: 995–999. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11535553
Setiawan VW, Yang HP, Pike MC, McCann SE, Yu H, et al. Type I and II endometrial cancers: Have they different risk factors? J Clin Oncol. 2013; 31: 2607–2618. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23733771
Dong C, Chen L. Second malignancies after breast cancer: The impact of adjuvant therapy. Mol Clin Oncol. 2014; 2: 331–336. PubMed: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3999127/
Levi F, Randimbison L, Te VC, La Vecchia C. Prognosis of bilateral synchronous breast cancer in Vaud, Switzerland. Breast. 2003; 12: 89–91. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/14659336
Ngô C, Brugier C, Plancher C, De La Rochefordière A, Alran S, et al. Clinico-pathology and prognosis of endometrial cancer in patients previously treated for breast cancer, with or without tamoxifen: A comparative study in 363 patients. Eur J Surg Oncol. 2014; 40: 1237–1244. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25086993
Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol. 2004; 94: 256–266. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15297160
Davies C, Pan H, Godwin J, Gray R, Arriagada R, et al. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. Lancet. 2013; 381: 805–816. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23219286
Van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrere CH, et al. Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994; 343: 448–452. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/7905955
Salani R, Andersen BL. Gynecologic care for breast cancer survivors: Assisting in the transition to wellness. Am J Obstet Gynecol. 2012; 206: 390–397. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/22177185
Wickerham DL, Fisher B, Wolmark N, Bryant J, Costantino J, et al. Association of tamoxifen and uterine sarcoma. J Clin Oncol. 2002; 20: 2758–2760. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12039943
Magriples U, Naftolin F, Schwartz PE, Carcangiu ML. High-grade endometrial carcinoma in tamoxifen-treated breast cancer patients. J Clin Oncol. 1993; 11: 485–490. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8383191
Swerdlow AJ, Jones ME. Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study. J Natl Cancer Inst. 2005; 97: 375–384. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15741574
Ascunze Elizaga N, González Enríquez J, González Navarro A, Herranz Fernández C, Marqués Bravo A, et al. Criterios generales y recomendaciones para la elaboracion de programas de deteccion precoz de cáncer de mama y cáncer de cérvix uterino en España. Rev San Hig Púb. 1993; 67: 23–37.