Clinical Review

Is Your Patient at High Risk for Breast Cancer?

Clinician Reviews. 2008 October;18(10):19-20

Author(s):

High-risk breast cancer assessment and management are key components of comprehensive women’s health care. Careful assessment and thorough history taking, diagnostic screening and risk reduction recommendations, referrals to specialists, and extensive patient education are all components of high-risk management. Primary health care clinicians may not deliver the services required, but a knowledge base in this complex area of women’s health will benefit both providers and their patients.

References

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Some 200,000 women in the United States are diagnosed with breast cancer each year. Among them, 15% to 20% have a family history of breast cancer and/or other cancers, and an additional 5% to 10% have a hereditary form of the disease.¹ Although great strides are being taken in the early detection and treatment of breast cancer, this disease remains the second leading cause of cancer deaths among women.

Equally important to early detection and improved treatment options is an understanding of factors that increase women’s risk for breast cancer, and the identification and management of women at increased risk—as well as identifying women who should be referred for high-risk evaluation and management. Interventions that limit the risk, whether offered by the primary care provider or a breast cancer specialist, can ultimately prevent some breast cancers from developing.

Risk assessment for breast cancer and an overview of high-risk evaluation and management provide the basis for this article.

Risk Factors
A variety of factors—some modifiable, some not—increase a woman’s risk for breast cancer (see Table 1²). Factors associated with particularly increased risk include:

• Family history of breast cancer in a first-degree relative or of breast or ovarian cancer in two or more close relatives^1-3

• Prior breast biopsy findings that revealed atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), or lobular carcinoma in situ (LCIS)

• Personal or family history of a BRCA1 or BRCA2 mutation

• Having undergone radiation to the chest wall between ages 10 and 30

• Personal or family history of other rare hereditary breast cancer syndromes,⁴ such as Cowden syndrome, Li-Fraumeni syndrome, or Peutz-Jeghers syndrome.^5-7

To understand high-risk factors in the overall context of breast cancer, it is important to understand the differences between sporadic, familial, and hereditary cancers. The majority of breast cancers, approximately 70%, occur sporadically.⁸ Sporadic cancers may be caused by random events occurring among or within cells, radiation exposure, or environmental or other unknown factors.

Among breast cancers, 15% to 20% are familial^8,9—ie, a recognized pattern of cancers occurs in the patient’s family, but affected members have tested negative for known genetic mutations. Familial cancers may be influenced by not-yet-identified genetic mutations or by environmental factors. As families usually share the same environment, dietary habits, and lifestyles, there may be an association between those factors and families with a cancer history.

Anyone who has a personal or family history of a mutation in either of the breast or ovarian cancer susceptibility genes, BRCA1 and BRCA2, has a significant risk for breast cancer. These are hereditary autosomal dominant mutations, inherited from an affected parent. Hereditary cancer syndromes, such as those associated with BRCA1 or BRCA2, are relatively rare. Only 5% to 10% of breast cancers are considered hereditary; of those, approximately 80% are related to mutations in BRCA1 or BRCA2.¹⁰

Several “red flags” suggest the possibility of a hereditary type of breast cancer syndrome. Genetic risk is primarily identified through thorough history taking, which must address both the maternal and paternal sides of the family—over three generations, if possible.¹⁰Table 2^10-14 identifies these red flags.

Atypical cells identified on breast biopsy also increase breast cancer risk. The presence of ADH or ALH increases a woman’s risk four to five times higher than the average.² LCIS is associated with a 10-fold increase in breast cancer risk.⁹ The overall incidence of breast cancer in women with LCIS is estimated at 22.3%.³

Radiation exposure to the chest wall, particularly when administered between ages 10 and 30, also increases the risk for breast cancer. This usually occurs in female patients who have undergone mantle-field radiation treatment for another cancer, such as Hodgkin’s disease or non-Hodgkin’s lymphoma.^15,16 Risk associated with this type of treatment can be as great as 12 times the normal risk. Patients treated before or during adolescence appear to be at highest risk.² Persons exposed to other types of radiation (eg, survivors of atomic weapons) also have increased breast cancer risk.¹

Rare genetic syndromes not associated with BRCA1 or BRCA2 have been associated with breast cancer as well. Cowden, Li-Fraumeni, and Peutz-Jeghers syndromes are all known hereditary breast cancer syndromes.^4-7 Although these syndromes account for less than 1% of all breast cancers,¹⁰ it is important to be able to identify a patient who is at risk for harboring a genetic mutation that causes one of these syndromes—and to understand how to manage a woman who is already affected.

Cowden syndrome is an autosomal dominant disorder caused by a mutation in the PTEN gene.^4,17 This syndrome carries a 25% to 50% risk for breast cancer.¹⁸ Other findings associated with Cowden syndrome include facial or buccal lesions, fibrocystic breast disease, benign thyroid conditions (eg, goiter), nonmedullary thyroid cancer, endometrial cancer, macrocephaly, uterine fibroids, and gastrointestinal hamartomas.^3,10