Download PDF
CC BY 4.0 · Rev Bras Ginecol Obstet 2021; 43(08): 638-643
DOI: 10.1055/s-0041-1736211
Febrasgo Position Statement

Hereditary determinants of gynecological cancer and recommendations

Number 8 - August 2021
Jesus Paula Carvalho 
1   Universidade de São Paulo, São Paulo, SP, Brazil
,
Filomena Marino Carvalho 
2   Universidade de São Paulo, São Paulo, SP, Brazil
,
Anisse Marques Chami 
3   Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
,
Agnaldo Lopes da Silva Filho 
4   Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
,
Walquíria Quida Salles Pereira Primo 
5   Universidade de Brasília, Brasília, DF, Brazil
› Author Affiliations
› Further Information
   Permissions and Reprints

Key points

  • Hereditary genetic factors are responsible for a considerable part of gynecological malignancies.

  • Knowing these factors enables precision prevention.

  • Non-HPV-associated cervical adenocarcinomas (NHPVA) are diseases related to hereditary genetic factors.

  • Among endometrial carcinomas, 3%-5% are hereditary (Lynch syndrome) and in half of cases they precede colorectal cancer, which is the most detected.

  • Ovarian, tubal and peritoneal high-grade serous carcinomas originate in the epithelium of the tubal fimbriae.

  • Approximately 20% of ovarian carcinomas are hereditary.

  • Pathogenic mutations of BRCA1 and BRCA2 genes are more frequent in ovarian cancer, but other genes are also related to this disease.

  • The identification of individuals at hereditary risk for gynecological cancer and prophylaxis are the most efficient measures.

  • Assessment of family history and appropriate genetic tests interpreted by qualified professionals are cost-effective.

  • Clinical therapeutic measures and prophylactic surgeries are part of the resources for prevention of hereditary gynecological cancer.

The National Specialty Commission for Gynecologic Oncology of the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO) endorses to this document. The content production is based on scientific studies on a thematic proposal and the findings presented contribute to clinical practice.




Publication History

Article published online:
21 September 2021

© 2021. Federação Brasileira de Ginecologia e Obstetrícia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

 

  • References

  • 1 Evans O, Gaba F, Manchanda R. Population-based genetic testing for Women's cancer prevention. Best Pract Res Clin Obstet Gynaecol 2020; 65: 139-53
    CrossrefPubMedSearch in Google Scholar
  • 2 Carvalho JP, Baracat EC, Carvalho FM. Ovarian cancer previvors: how to manage these patients? Clinics (Sao Paulo). 2019; 74: e1343
    CrossrefPubMedSearch in Google Scholar
  • 3 Walboomers JM, Jacobs MV, Manos MM, Bosch FX, Kummer JA, Shah KV. et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol. 1999; 189 (01) 12-9
    CrossrefPubMedSearch in Google Scholar
  • 4 Stolnicu S, Barsan I, Hoang L, Patel P, Terinte C, Pesci A. et al. International Endocervical Adenocarcinoma Criteria and Classification (IECC): a new pathogenetic classification for invasive adenocarcinomas of the endocervix. Am J Surg Pathol 2018; 42 (02) 214-26
    CrossrefPubMedSearch in Google Scholar
  • 5 Stolnicu S, Hoang L, Soslow RA. Recent advances in invasive adenocarcinoma of the cervix. Virchows Arch 2019; 475 (05) 537-49
    CrossrefPubMedSearch in Google Scholar
  • 6 Carnevali I, Di Lauro E, Pensotti V, Sahnane N, Leoni E, Formenti G. et al. HPV nonrelated endocervical adenocarcinoma in hereditary cancer syndromes. Tumori 2020; 106 (06) NP67-NP72
    CrossrefPubMedSearch in Google Scholar
  • 7 Antill YC, Dowty JG, Win AK, Thompson T, Walsh MD, Cummings MC. et al. Lynch syndrome and cervical cancer. Int J Cancer 2015; 137 (11) 2757-61
    CrossrefPubMedSearch in Google Scholar
  • 8 Nair N, Curtin JP, Mittal K, Hiotis KL. Cervical adenocarcinoma in a patient with Lynch syndrome, Muir-Torre variant. J Clin Oncol 2012; 30 (02) e5-6
    CrossrefPubMedSearch in Google Scholar
  • 9 Morgan S, Slodkowska E, Parra-Herran C, Mirkovic J. PD-L1, RB1 and mismatch repair protein immunohistochemical expression in neuroendocrine carcinoma, small cell type, of the uterine cervix. Histopathology 2019; 74 (07) 997-1004
    CrossrefPubMedSearch in Google Scholar
  • 10 Weber W, De Sabata MS, Paredes RM, Rodriguez G, Santos C, Sabillon JU. et al. Cancer in first degree relatives of Latin American women with cervical cancer. A pilot study. Anticancer Res 2005; 25 (2B): 1219-23
    PubMedSearch in Google Scholar
  • 11 Chintalacheruvu LM, Shaw T, Buddam A, Diab O, Kassim T, Mukherjee S. et al. Major hereditary gastrointestinal cancer syndromes: a narrative review. J Gastrointestin Liver Dis 2017; 26 (02) 157-63
    CrossrefPubMedSearch in Google Scholar
  • 12 Møller P, Seppälä TT, Bernstein I, Holinski-Feder E, Sala P, Gareth Evans D. et al. Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database. Gut 2018; 67 (07) 1306-16
    CrossrefPubMedSearch in Google Scholar
  • 13 Snowsill TM, Ryan NA, Crosbie EJ. Cost-effectiveness of the Manchester approach to identifying Lynch Syndrome in women with endometrial cancer. J Clin Med 2020; 9 (06) 1664
    CrossrefPubMedSearch in Google Scholar
  • 14 Anagnostopoulos A, McKay VH, Cooper I, Campbell F, Greenhalgh L, Kirwan J. Identifying Lynch Syndrome in women presenting with endometrial carcinoma under the age of 50 years. Int J Gynecol Cancer 2017; 27 (05) 931-7
    CrossrefPubMedSearch in Google Scholar
  • 15 Dörk T, Hillemanns P, Tempfer C, Breu J, Fleisch MC. Genetic susceptibility to endometrial cancer: risk factors and clinical management. Cancers (Basel) 2020; 12 (09) 2407
    CrossrefPubMedSearch in Google Scholar
  • 16 de Jonge MM, Mooyaart AL, Vreeswijk MP, de Kroon CD, van Wezel T, van Asperen CJ. et al. Linking uterine serous carcinoma to BRCA1/2-associated cancer syndrome: a meta-analysis and case report. Eur J Cancer 2017; 72: 215-25
    CrossrefPubMedSearch in Google Scholar
  • 17 Mester J, Eng C. Cowden syndrome: recognizing and managing a not-so-rare hereditary cancer syndrome. J Surg Oncol 2015; 111 (01) 125-30
    CrossrefPubMedSearch in Google Scholar
  • 18 Tan MH, Mester JL, Ngeow J, Rybicki LA, Orloff MS, Eng C. Lifetime cancer risks in individuals with germline PTEN mutations. Clin Cancer Res 2012; 18 (02) 400-7
    CrossrefPubMedSearch in Google Scholar
  • 19 Walsh T, Casadei S, Lee MK, Pennil CC, Nord AS, Thornton AM. et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing. Proc Natl Acad Sci USA 2011; 108 (44) 18032-7
    CrossrefPubMedSearch in Google Scholar
  • 20 Thompson D, Easton DF. Breast Cancer Linkage Consortium. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002; 94 (18) 1358-65
    CrossrefPubMedSearch in Google Scholar
  • 21 Kitson SJ, Bafligil C, Ryan NA, Lalloo F, Woodward ER, Clayton RD. et al. BRCA1 and BRCA2 pathogenic variant carriers and endometrial cancer risk: a cohort study. Eur J Cancer 2020; 136: 169-75
    CrossrefPubMedSearch in Google Scholar
  • 22 Dominguez-Valentin M, Seppälä TT, Engel C, Aretz S, Macrae F, Winship I. et al. Risk-reducing gynecological surgery in Lynch Syndrome: results of an International Survey from the Prospective Lynch Syndrome Database. J Clin Med 2020; 9 (07) 2290
    CrossrefPubMedSearch in Google Scholar
  • 23 Shu CA, Pike MC, Jotwani AR, Friebel TM, Soslow RA, Levine DA. et al. Uterine cancer after risk-reducing salpingo-oophorectomy without hysterectomy in women with BRCA mutations. JAMA Oncol 2016; 2 (11) 1434-40
    CrossrefPubMedSearch in Google Scholar
  • 24 Mejia-Gomez J, Gronwald J, Senter L, Karlan BY, Tung N, Wolfman W. et al. Factors associated with use of hormone therapy after preventive oophorectomy in BRCA mutation carriers. Menopause 2020; 27 (12) 1396-402
    CrossrefPubMedSearch in Google Scholar
  • 25 Furness S, Roberts H, Marjoribanks J, Lethaby A. Hormone therapy in postmenopausal women and risk of endometrial hyperplasia. Cochrane Database Syst Rev 2012; 2012 (08) CD000402
    CrossrefPubMedSearch in Google Scholar
  • 26 Kotsopoulos J, Gronwald J, Karlan BY, Huzarski T, Tung N, Moller P. et al. Hormone replacement therapy after oophorectomy and breast cancer risk among BRCA1 mutation carriers. JAMA Oncol 2018; 4 (08) 1059-65
    CrossrefPubMedSearch in Google Scholar
  • 27 National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Genetic/Familial High-Risk Assessment: breast and ovarian: Version 3.2019 [Internet]. 2019 [cited 2021 May 6]. p. 5. Available from: https://www2.tri-kobe.org/nccn/guideline/gynecological/english/genetic_familial.pdf
    PubMedSearch in Google Scholar
  • 28 Yoshida R. Hereditary breast and ovarian cancer (HBOC): review of its molecular characteristics, screening, treatment, and prognosis. Breast Cancer. 2020 Aug 2929. doi:10.1007/s12282-020-01148-2. [ahead of print].
    PubMedSearch in Google Scholar
  • 29 Boyarskikh UA, Gulyaeva LF, Avdalyan AM, Kechin AA, Khrapov EA, Lazareva DG. et al. Spectrum of TP53 mutations in BRCA1/2 associated high-grade serous ovarian cancer. Front Oncol 2020; 10: 1103
    CrossrefPubMedSearch in Google Scholar
  • 30 Labidi-Galy SI, Papp E, Hallberg D, Niknafs N, Adleff V, Noe M. et al. High grade serous ovarian carcinomas originate in the fallopian tube. Nat Commun 2017; 8 (01) 1093
    CrossrefPubMedSearch in Google Scholar
  • 31 Steenbeek MP, Bulten J, Snijders MP, Lombaers M, Hendriks J, van den Brand M. et al. Fallopian tube abnormalities in uterine serous carcinoma. Gynecol Oncol 2020; 158 (02) 339-46
    CrossrefPubMedSearch in Google Scholar
  • 32 Chen EY, Mehra K, Mehrad M, Ning G, Miron A, Mutter GL. et al. Secretory cell outgrowth, PAX2 and serous carcinogenesis in the Fallopian tube. J Pathol 2010; 222 (01) 110-6
    CrossrefPubMedSearch in Google Scholar
  • 33 Diniz PM, Carvalho JP, Baracat EC, Carvalho FM. Fallopian tube origin of supposed ovarian high-grade serous carcinomas. Clinics (Sao Paulo) 2011; 66 (01) 73-6
    CrossrefPubMedSearch in Google Scholar
  • 34 Wu NY, Fang C, Huang HS, Wang J, Chu TY. Natural history of ovarian high-grade serous carcinoma from time effects of ovulation inhibition and progesterone clearance of p53-defective lesions. Mod Pathol 2020; 33 (01) 29-37
    CrossrefPubMedSearch in Google Scholar
  • 35 Menon U, Gentry-Maharaj A, Hallett R, Ryan A, Burnell M, Sharma A. et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol 2009; 10 (04) 327-40
    CrossrefPubMedSearch in Google Scholar
  • 36 Hart SN, Polley EC, Yussuf A, Yadav S, Goldgar DE, Hu C. et al. Mutation prevalence tables for hereditary cancer derived from multigene panel testing. Hum Mutat 2020; 41 (08) e1-6
    CrossrefPubMedSearch in Google Scholar
  • 37 Gaba F, Robbani S, Singh N, McCluggage WG, Wilkinson N, Ganesan R. et al. Preventing ovarian cancer through early excision of tubes and late ovarian removal (PROTECTOR): protocol for a prospective non-randomised multi-center trial. Int J Gynecol Cancer 2021; 31 (02) 286-91
    CrossrefPubMedSearch in Google Scholar
  • 38 Garcia C, Wendt J, Lyon L, Jones J, Littell RD, Armstrong MA. et al. Risk management options elected by women after testing positive for a BRCA mutation. Gynecol Oncol 2014; 132 (02) 428-33
    CrossrefPubMedSearch in Google Scholar
  • 39 Rhiem K, Foth D, Wappenschmidt B, Gevensleben H, Büttner R, Ulrich U. et al. Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers. Arch Gynecol Obstet 2011; 283 (03) 623-7
    CrossrefPubMedSearch in Google Scholar
  • 40 Wilhite AM, Oestreich MC, Olson M, Bedell SM, Westenberg D, Bangdiwala A. et al. Health care provider adherence to surgical guidelines for risk-reducing salpingo-oophorectomy. Obstet Gynecol 2019; 134 (03) 520-6
    CrossrefPubMedSearch in Google Scholar
  • 41 Correa-Galendi JS, Diz MP, Stock S, Müller D. Economic modelling of screen-and-treat strategies for Brazilian women at risk of hereditary breast and ovarian cancer. Appl Health Econ Health Policy 2021; 19 (01) 97-109
    CrossrefPubMedSearch in Google Scholar