Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families

Tadeusz Dębniak; Tomasz Gromowski; Rodney J Scott; Jacek Gronwald; Tomasz Huzarski; Tomasz Byrski; Grzegorz Kurzawski; Dagmara Dymerska; Bohdan Górski; Katarzyna Paszkowska-Szczur; Cezary Cybulski; Pablo Serrano-Fernandez; Jan Lubiński

doi:10.1186/s13053-015-0025-2

Management of ovarian and endometrial cancers in women belonging to HNPCC carrier families: review of the literature and results of cancer risk assessment in Polish HNPCC families

Hered Cancer Clin Pract. 2015 Jan 16;13(1):3. doi: 10.1186/s13053-015-0025-2. eCollection 2015.

Affiliations

¹ Department o f Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland.
² Discipline of Medical Genetics, Faculty of Health, University of Newcastle and Hunter Medical Research Institute, Newcastle, NSW Australia.

Abstract

Background: Over half the cancer deaths in HNPCC families are due to extra-colonic malignancies that include endometrial and ovarian cancers. The benefits of surveillance for gynecological cancers are not yet proven and there is no consensus on the optimal surveillance recommendations for women with MMR mutations.

Methods: We performed a systematic review of the literature and evaluated gynecological cancer risk in a series of 631 Polish HNPCC families classified into either Lynch Syndrome (LS, MMR mutations detected) or HNPCC (fulfillment of the Amsterdam or modified Amsterdam criteria).

Results: Published data clearly indicates no benefit for ovarian cancer screening in contrast to risk reducing surgery. We confirmed a significantly increased risk of OC in Polish LS families (OR = 4,6, p < 0.001) and an especially high risk of OC was found for women under 50 years of age: OR = 32,6, p < 0.0001 (95% CI 12,96-81,87). The cumulative OC risk to 50 year of life was calculated to be 10%. Six out of 19 (32%) early-onset patients from LS families died from OC within 2 years of diagnosis. We confirmed a significantly increased risk of EC (OR = 26, 95% CI 11,36-58,8; p < 0,001). The cumulative risk for EC in Polish LS families was calculated to be 67%.

Conclusions: Due to the increased risk of OC and absence of any benefit from gynecological screening reported in the literature it is recommended that prophylactic oophorectomy for female carriers of MMR mutations after 35 year of age should be considered as a risk reducing option. Annual transvaginal ultrasound supported by CA125 or HE4 marker testing should be performed after prophylactic surgery in these women. Due to the high risk of EC it is reasonable to offer, after the age of 35 years, annual clinical gynecologic examinations with transvaginal ultrasound supported by routine aspiration sampling of the endometrium for women from either LS or HNPCC families. An alternative option, which could be taken into consideration for women preferring surgical prevention, is risk reducing total hysterectomy (with bilateral salpingo-oophorectomy) for carriers after childbearing is complete.

Keywords: Adnexectomy; Endometrial cancer; HNPCC; Lynch syndrome; Ovarian cancer.