Research Article

Gynaecological malignancies after breast cancer diagnosis: A population-based study

Maria Pilar Barretina-Ginesta, Jaume Galceran*, Helena Pla, Cristina Meléndez, Anna Carbo Bague, Alberto Ameijide, Marià Carulla, Jordi Barretina, Angel Izquierdo and Rafael Marcos-Gragera

Published: 31 October, 2019 | Volume 2 - Issue 2 | Pages: 113-118

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.

Read Full Article HTML DOI: 10.29328/journal.cjog.1001031 Cite this Article Read Full Article PDF


Breast cancer; Gynaecological malignancies; Second primary cancer; Standardized incidence ratio


  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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
  11. 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
  12. 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
  13. 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
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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/
  21. 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
  22. 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
  23. Cohen I. Endometrial pathologies associated with postmenopausal tamoxifen treatment. Gynecol Oncol. 2004; 94: 256–266. PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15297160
  24. 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
  25. 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
  26. 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
  27. 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
  28. 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
  29. 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
  30. 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.

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