Devita, Hellman, and Rosenberg's Cancer

LWBK1006-14 LWW-Govindan-Review November 24, 2011 11:28

158 DeVita, Hellman, and Rosenberg’s CANCER: Principles and Practice of Oncology Review

Answer 14.8. The answer is A.

BSO in BRCA carriers is the most effective procedure to reduce the risk of

ovarian cancer and is generally recommended upon completion of child-

bearing. BSO also decreases the risk of subsequent breast cancer.

Answer 14.9. The answer is B.

Missense variants result in the substitution of one amino acid for another.

These variants occur frequently in theBRCA1andBRCA2genes. The

functional significance cannot be determined with gene sequencing alone.

Functional analysis of the BRCA1 and BRCA2 proteins is not available.

Angela has a 50% probability to have theBRCA2gene variant, but

because the functional significance is unknown, testing Angela does not

provide any clinically relevant information for her. Furthermore, because

Angela has not been diagnosed with cancer, genetic analysis does not

provide any new information to clarify Jennifer’s test results. If Angela

had been diagnosed with early-onset breast cancer, then analysis for the

BRCA2gene variant would have been offered for research purposes only

to help determine whether the variant is tracking with disease in the

family.

For this family, genetic testing did not provide any new information

to facilitate their medical decision making. Individuals with these types

of gene variants are often left intellectually and emotionally frustrated

by the testing. Imagine deciding to pursue expensive genetic testing with

the intention of using the results to guide your personal and family med-

ical care only to learn the testing provides no clear answer. As clinical

genetic testing quickly becomes available following gene discovery, clini-

cians must contend with the identification of variants of unknown func-

tional significance. The development of functional, rather than descrip-

tive, testing will help to address this challenging clinical issue. Until such

techniques are developed, it is important to inform individuals of the

possibility of identifying these types of variants of unknown before the

initiation of genetic testing.

Answer 14.10. The answer is C.

Breast cancer in BRCA2 carriers is usually ER positive and these patients

are at risk of developing second primaries, with the risk decreasing to

less than 10% after prophylactic bilateral mastectomy. Treatment with

tamoxifen decreases the risk of contralateral breast cancer in BRCA2

carriers.

Answer 14.11. The answer is C.

Pauline’s testing is uninformative because the underlying genetic basis for

cancer predisposition has not yet been identified in her family. When pos-

sible, genetic testing should always begin with an affected family member.

In essence, when evaluating a family with genetic disease, testing should

begin with the person who expresses features of the inherited condition.

In the case of hereditary cancer syndromes, expression is defined as a per-

son who is diagnosed with one of the associated malignancies or benign