Hereditary gynaecological cancer syndromes — structured SAQ (15 marks)

FRANZCOG-format structured SAQ on HBOC: pedigree and Manchester scoring, BRCA1/BRCA2 penetrance figures from source, the timing and technique of risk-reducing salpingo-oophorectomy, and counselling around surgical menopause and HRT. Per-sub-part marking rubric included.

Prompt

A 37-year-old woman, G2P2, is referred following the diagnosis of high-grade serous ovarian cancer in her 43-year-old sister. Her mother had breast cancer at 48 and a maternal aunt had triple-negative breast cancer at 39. The patient herself is well. She asks whether she 'has the gene' and what she should do. (a) Construct a focused three-generation family history and state how you would convert it into a decision to test, naming a validated scoring system and its threshold. (4 marks) (b) Outline the lifetime ovarian and breast cancer risks for a confirmed BRCA1 carrier, citing the prospective cohort estimates to age 80, and contrast these with a BRCA2 carrier. (4 marks) (c) If she is confirmed to carry a pathogenic BRCA1 variant, detail your recommendation for risk-reducing surgery: the operation, its timing, the intraoperative pathological requirements, and what the surgery does and does not prevent. (4 marks) (d) Address the consequences of surgical menopause and the place of hormone replacement therapy. (3 marks)

How this SAQ is marked

Twelve SAQs, 180 marks, two 2-hour papers — roughly 15 marks and 20 minutes each. Marks come from specifics: the named score and its threshold, the gene-specific risk figure with its age horizon, the operation named precisely, and the honest statement of what surgery does not prevent. Write in short labelled points. Answer the sub-part asked. ^[1]

Reveal model answer and mark schemeShow

(a) Family history and decision to test (4 marks)

Three-generation pedigree, maternal and paternal lines, affected and unaffected relatives with age at diagnosis (sister HGSOC 43, mother breast 48, maternal aunt triple-negative breast 39). (1)
Pattern fits hereditary breast and ovarian cancer: ovarian cancer at any age + early/bilateral/triple-negative breast cancer. (1)
Convert to a Manchester score (Evans 2004): points by cancer type, age, pathology; a score of 10 points for a gene equates to ~10% probability of a pathogenic variant — the threshold at which testing is offered. (1) ^[5]
This family clearly exceeds threshold; offer a germline multigene panel (NGS with deletion/duplication analysis). (1)

(b) Risk figures (4 marks)

BRCA1 ovarian risk to age 80 ~44% (95% CI 36-53%); BRCA2 ~17% (11-25%) — Kuchenbaecker prospective cohort. (2) ^[1]
Breast risk to age 80 ~72% (BRCA1) and ~69% (BRCA2); contralateral breast risk markedly elevated. (1)
Age-70 meta-analytic estimates (Chen-Parmigiani) give BRCA1 ovarian ~40%, BRCA2 ~18% — the horizon (70 vs 80) explains the difference, not contradiction. (1) ^[2]

(c) Risk-reducing surgery (4 marks)

Risk-reducing bilateral salpingo-oophorectomy between age 35 and 40 for a BRCA1 carrier (BRCA2 timing is 40-45), after childbearing. (1) ^[11]
Operation is not a 'simple' BSO: send peritoneal washings, inspect peritoneal surfaces, remove tubes and ovaries entire, SEE-FIM pathology (sectioning and extensively examining the fimbriated end) to detect occult STIC. (1)
Prevents ovarian/fallopial-tube cancer and most peritoneal cancer; reduces cancer-specific and overall mortality (Finch/Domchek). (1) ^[3]
Does not prevent all primary peritoneal carcinoma (residual risk, especially if occult STIC present) and does not abolish breast cancer risk. (1)

(d) Surgical menopause and HRT (3 marks)

RRSO at 37 induces premature surgical menopause — bone, cardiovascular and vasomotor consequences. (1)
HRT is recommended up to the age of natural menopause (~50); short-term HRT after premenopausal RRSO does not negate the breast-risk benefit of surgery. (1) ^[3]
Withholding HRT to 'protect the breasts' is an error; coordinate breast MRI surveillance (from 25-30) and familial cancer service follow-up. (1)

References5Show

[1]Kuchenbaecker KB, Hopper JL, Barnes DR, et al. Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers JAMA, 2017.PMID 28632866
[2]Chen S, Parmigiani G Meta-analysis of BRCA1 and BRCA2 penetrance J Clin Oncol, 2007.PMID 17416853
[3]Finch AP, Lubinski J, Møller P, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation J Clin Oncol, 2014.PMID 24567435
[5]Evans DG, Eccles DM, Rahman N, et al. A new scoring system for the chances of identifying a BRCA1/2 mutation outperforms existing models including BRCAPRO J Med Genet, 2004.PMID 15173236
[11]Sabiani L, Barrou J, Mathis J, Eisinger F How to manage BRCA mutation carriers? Horm Mol Biol Clin Investig, 2020.PMID 32459193