Gynecologic Cancer

“Chance and bias may cause erroneous results and inflated expectations in the kind of observational research being conducted in several ‘–omics’ fields to assess molecular markers for diagnosis and prognosis of cancer. To realize the potential of new –omics technology will require appropriate rules of evidence in the design, conduct, and interpretation of the clinical research,” writes Dr. Ransohoff.

While proteomic profiling clearly has promise, clinicians should insist that initial studies be validated

What to tell patients. I explain that the test appeared promising, and therefore was of great interest, but the FDA did not allow it to be put on the market because of insufficient evidence that the test consistently defines whether cancer is or is not present. Since either a negative or positive test would have profound effects, accuracy is an absolute requirement.

RELATED REFERENCES

• Baggerly KA, Morris JS, Edmonson SR, Coombes KR. Signal in noise: evaluating reported reproducibility of serum proteomic tests for ovarian cancer. J Natl Cancer Inst. 2005;97:307–309.
• Liotta LA, Lowenthal M, Mehta A, et al. Importance of communication between producers and consumers of publicly available experimental data. J Natl Cancer Inst. 2005;97:310–314.
• Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet. 2002;359:572–577.

Don’t hold back from counseling risk-reducing BSO when indicated

Metcalfe KA, Lynch HT, Ghadirian P, et al. The risk of ovarian cancer after breast cancer in BRCA1 and BRCA2 carriers. Gynecol Oncol. 2005;96:222–226.

Counsel women with breast cancer who are BRCA1 or BRCA2 mutation carriers to consider prophylactic salpingo-oophorectomy after childbearing is complete. Tamoxifen and chemotherapy do not lower risk.

ObGyns should encourage young women with breast cancer or women with a strong family history of breast and/or ovarian cancer to undergo genetic testing.

Women with breast cancer who are found to be BRCA1 or BRCA2 mutation carriers should be counseled by their gynecologists to consider prophylactic BSO after childbearing is complete. Even though these women’s greatest concern may be breast cancer recurrence, gynecologists should advise these women that they are also at risk for ovarian cancer, and that they can substantially decrease their risk by undergoing risk-reduction surgery. BRCA1 mutation carriers have up to an 80% lifetime risk of breast cancer and up to a 50% lifetime risk for ovarian cancer.

Recent data support intervention to decrease risk: BSO decreases risk of ovarian cancer by more than 90%, and decreases risk of breast cancer by 50% in BRCA1 or BRCA2 mutation carriers. Metcalfe et al examined women with a BRCA1 or BRCA2 mutation and a history of stage I or II breast cancer, and found that 10% developed an ovarian cancer, a fallopian tube cancer, or a peritoneal cancer. The median time was 8.1 years from the development of breast cancer to the development of ovarian cancer. The cumulative risk of developing ovarian cancer after breast cancer was 12.7% for BRCA1 mutation carriers and 6.8% for BRCA2 mutation carriers.

Tamoxifen or chemotherapy did not change this risk. The authors concluded that BSO could have prevented at least 43 to 46 ovarian cancers.

RELATED REFERENCES

• Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–1622.
• Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002; 346:1609–1615.

Serial histologic sectioning is vital for detecting occult malignancy

Powell CB, Kenley E, Chen LM, et al. Risk-reducing salpingo-oophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol. 2005;23:127–132.

A specific 4-step protocol for salpingo-oophorectomy and pathologic examination increased the number of occult malignancies identified.

Is a risk-reducing BSO any different from a BSO for benign reasons? The evidence is a resounding YES. Given the strong data supporting prophylactic BSO in women with BRCA1 or BRCA2 mutations, ObGyns are increasingly called upon to perform this procedure. Current recommendations are to offer surgery to mutation carriers after childbearing or in their mid- to late 30s and early 40s. A number of studies have discovered that carriers who undergo risk-reducing BSO are at increased risk for occult malignancies already existing in the ovaries and fallopian tubes.

These studies recommend use of a specific surgical approach and pathologic examination of specimens.