Secondary Prevention in Hereditary Breast and/or Ovarian Cancer Syndromes Other Than BRCA

Table 1

Summary of the recommendations for each predisposition gene.

Predisposition genes	Cancer risk	Lifetime risk	Surveillance
High-penetrance genes for breast and/or ovarian cancer
TP53	Adrenocortical gland	6–13% [25]	Ultrasound of abdomen and pelvis: every 3–4 mos, birth to age 18 yrs [27]
	Breast	54% [25]	Clinical breast examination: every 6–12 mos, age ≥ 20 yrs
			Breast MRI screening with contrast (with or without mammogram): annually, age 20–75 yrs [27]
	Central nervous system	6–19% [25]	Neurologic exam: annually, all ages
			Brain MRI: annually [27]
	Sarcomas	5–22% [25]	Whole-body MRI: annually, all ages
			Ultrasound of abdomen and pelvis: annually, age ≥18 yrs [27]
	Hematologic tumors	NA	Periodic blood test if increased risk for myelodysplastic syndrome or leukaemia [28]
	Gastrointestinal system	NA	Upper endoscopy and colonoscopy: every 2–5 yrs, age ≥25 yrs [27]
	Skin	NA	Dermatologic exam: annually, age ≥18 yrs [27]
PTEN	Breast	85% [5]	Clinical breast examination: every 6 mos, age ≥ 25 yrs
			Mammogram and breast MRI with contrast: annually, age 30–75 yrs [6]
	Thyroid	35% [36]	Ultrasound of thyroid: annually, all ages [6]
	Endometrium	28% [36]	Endometrial biopsy: every 1–2 yrs [6]
	Colon and rectum	9% [36]	Colonoscopy: every 5 yrs, age ≥ 35 yrs [6]
	Kidney	30% [36]	CT or MRI of abdomen: every 1–2 yrs, age ≥ 40 yrs [6]
	Melanoma	5% [38]	Dermatologic exam: annually, age ≥18 yrs [38]
CDH1	Stomach	56–83% [8]	Upper endoscopy: every 6–12 mos, age ≥ 18 yrs [59]
	Breast	52% [8]	Mammogram and breast MRI with contrast: annually, age ≥ 30 yrs [6]
STK11	Colon and rectum	39% [9]	Colonoscopy: every 2–3 yrs, age ≥ 18 yrs [61]
	Stomach	29% [9]	Upper endoscopy: every 2–3 yrs, age ≥ 18 yrs [61]
	Small bowel	13% [9]	Capsule endoscopy: every 2–3 yrs, age ≥ 18 yrs [61]
	Pancreas	11–36% [9]	MR cholangiopancreatography with contrast or endoscopic ultrasound: every 1–2 yrs, age ≥ 30 yrs [62]
	Breast	32–54% [9]	Clinical breast examination: every 6 mos, age ≥ 20 yrs
			Mammogram and breast MRI with contrast: annually, age ≥ 25 yrs [6]
	Ovary, cervix, and uterus	9–21% [9]	Transvaginal ultrasound, serum CA 125, pelvic exam with pap smear: annually, age ≥ 18 yrs [6]
	Testis	9% [9]	Testicular exam: annually, until 18 yrs [62]
	Lung	7–17% [9]	Not recommended
Low-/moderate-penetrance genes for breast and/or ovarian cancer
PALB2	Breast	35% [69]	Mammogram and breast MRI with contrast: annually, age ≥ 30 yrs [6]
	Ovary, pancreas	NA	Not recommended
CHEK2	Breast	28–37% [13, 75]	Mammogram and breast MRI with contrast: annually, age ≥ 40 yrs [6]
	Colon	NA	Colonoscopy: every 5 yrs, age ≥ 40 yrs [6]
	Prostate, kidney, bladder, and thyroid	NA	Not recommended
NBN (675del5)	Breast	Up to 30% [77]	Breast MRI with contrast: annually, age ≥ 40 yrs [6]
	Ovary and prostate	NA	Not recommended
MLH1, MSH2, MSH6, PMS2, EPCAM	Colon and rectum	48–57% [43]	Colonoscopy: every 1-2 yrs, age ≥ 20–25 yrs [6]
	Endometrium	43–57% [43]	Not recommended
	Ovary	Up to 24% [43]	Not recommended
	Stomach, small bowel	4–13% [43]	Upper endoscopy: every 3–5 yrs, age ≥ 40 yrs if relevant family history or mutation in MLH1, MSH2 or EPCAM [45, 51]
	Hepatobiliary tract	Up to 4% [43]	In research protocol [6]
	Urinary tract	Up to 25% [43]	Urinalysis: annually, age ≥ 30–35 yrs if relevant family history or MSH2 mutation [6]
	Brain	1–4% [43]	Physical and neurologic examination: annually, age ≥ 25–30 yrs [6]
	Breast (MSH2, MLH1, PMS2, or MSH6)	11–18% [53–55]	Not recommended
	Prostate	NA	Not recommended
ATM	Breast	33% [12]	Mammogram with consideration of breast MRI with contrast: annually, age ≥ 40 yrs [6]
	Ovary, prostate, and pancreas	NA	Not recommended
BRIP1, RAD51C, RAD51D	Ovary	Up to 10% [15]	Not recommended
NF1	Nervous system	8–16% [64]	Physical and eye examination: annually, every age [63, 64]
	Breast	17% [64]	Mammogram and breast MRI with contrast: annually, age 30–50 yrs [65]
BARD1	Breast	NA	Not recommended

NA = not available, Risk-reducing surgery can be considered based on type of mutation and family history.