Reducing the risk of breast cancer

Article Figures & Data

TABLE 1

Guidelines to evaluate for hereditary breast cancer

Age 50 or younger
Ovarian cancer (at any age)
Triple-negative breast cancer (at any age)
Male breast cancer (at any age)
Multiple primary breast cancers
Pancreatic cancer
Metastatic prostate cancer
Three or more diagnoses of breast cancer in the patient or a close blood relative
Two or more close (first-degree) relatives with breast or prostate cancer at any age
To aid in treatment decisions using poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors in patients with metastatic or very-high-risk breast cancer
Lobular breast cancer with a personal or family history of diffuse gastric cancer
Ashkenazi Jewish ancestry
Finding of a mutation in somatic tumor testing
A patient without a cancer diagnosis but with a first-, second-, or third-degree relative meeting the above criteria: Exceptions: 1) If patient is eligible for PARP inhibitors; 2) If patient meets testing criteria based only on pancreatic cancer or metastatic prostate cancer, the affected relative must be a first-degree relative

TABLE 2

An overview of tumor pathology in hereditary breast cancer

Gene with pathogenic variant	Estrogen-receptor–positive tumor	Estrogen-receptor–negative tumor	Triple-negative tumor
BRCA1	Increasingly positive after age 50	+++ particularly before age 50	+++ particularly before age 50
BRCA2	++	Over-representation,^a but still primarily estrogen-receptor–positive	Over-representation,^a but still primarily estrogen-receptor–positive
PALB2	++	Over-representation,^a but still primarily estrogen-receptor–positive	Over-representation,^a but still primarily estrogen-receptor–positive
ATM	+++
CHEK2	+++
CDH1	+++
TP53	+++
BARD1		+++	+++
RAD51C		+++	+++
RAD51D		+++	+++

↵a Estrogen receptor tumors are more common than in the general population but are still not the predominant type of tumor pathology.
+ = relative prevalence

TABLE 3

Medications used for breast cancer risk reduction: A brief summary of clinical trials

Trial	N	Eligibility	HR^a	HR^b	NNT
NSABP P-1 5-year trial Tamoxifen 20 mg vs placebo³³	13, 388	Pre- and post-menopausal; Gail model-estimated 5-year risk ≥ 1.66%	0.51	0.14 for AH; 0.44 for LCIS	22
IBIS-1 5-year trial Tamoxifen 20 mg vs placebo⁴⁸	7,154	Pre- and post- menopausal; 50% on hormone-replacement therapy	0.75; with long-term follow-up 0.71	Not stated	Not stated
STAR P-2 5-year trial Tamoxifen 20 mg vs raloxifene 60 mg^34,50	19,747	Postmenopausal	Equal at 5 years; with long-term follow-up; raloxifene = 0.62	Equal	Not stated (about 22)
MAP.3 3-year trial Exemestane 25 mg, exemestane 25 mg plus celecoxib, vs placebo⁴⁶	4,560	Postmenopausal	0.35	0.36 (for AH/LCIS combined)	26 at 5 years
IBIS II 5-year trial Anastrozole 1 mg vs placebo⁴⁷	3,864	Postmenopausal	0.47	0.31 (for AH/LCIS combined)	29^c
Low-dose tamoxifen 3-year trial Tamoxifen 5 mg vs placebo⁴⁹	500	Pre- and post menopausal; included patients with ductal carcinoma in situ	0.48	Not stated	22

↵a For reduction in invasive breast cancer.
↵b For reduction in invasive breast cancer in patients with AH and LCIS.
↵c To prevent 1 cancer in 7 years of follow-up, 36 women would need to be treated.
AH = atypical hyperplasia; HR = hazard ratio; IBIS = International Breast Cancer Intervention Study; LCIS = lobular carcinoma in situ; MAP = Mammary Prevention trial; NNT = number needed to treat; NSABP = National Surgical Adjuvant Breast and Bowel Project; STAR = Study of Tamoxifen and Raloxifene