Impact of BRCA1/BRCA2 Counseling and Testing on Newly Diagnosed Breast Cancer Patients
Background:
Even though only 5-10% of women diagnosed with breast cancer carry the BRCAJ or BRCA2 mutation, the presence of the mutation carries significant treatment considerations. The impact of genetic testing for women with inherited breast and ovarian cancer susceptibility has been mostly studied in cancer survivors and their family members. The impact that genetic testing has on women that have been newly diagnosed with breast cancer has not been extensively studied.
Objective:
To prospectively evaluate the influence of BRCAJ and BRCA2 genetic testing and counseling among patients newly diagnosed with breast cancer that are at high-risk of carrying the gene mutation, and their subsequent surgical decisions.
Methods:
One hundred and ninety-four patients with newly diagnosed breast cancer who were at high-risk of the BRCAJ/BRCA2 mutation were entered into the study. Criteria for genetic testing was determined by the Lombardi Comprehensive Cancer Center’s Assessment and Risk Evaluation program, which tries to identify women with at least a 10% chance of carrying the gene mutation. Eligible patients underwent a structured telephone interview followed by a 1.5-2 h genetic counseling session. Following the counseling session, the participants were offered genetic testing, and 27 participants (14%) declined this. Genetic testing results were available within 2-3 weeks. When tests results were available a disclosure session was performed which gave the participants the following results: (1) a deleterious mutation was identified (31 patients); (2) no mutation was identified (62 patients) but there was a possibly of a false negative result or a mutation in another gene; (3) ambiguous results (19 patients) which could not rule out hereditary breast cancer; and (4) Ashkenazi Jewish patients who tested negative for the founder probands (55 patients) and had a low-risk for the mutation. The following measures were gathered: sociodemographic and family history variables, stage at diagnosis, adjuvant chemotherapy, psychological variables, patients’ report of genetic testing recommendations, patients’ report of surgical recommendation and definitive treatment decision.
Results:
* Mean age of 43 years.
* Predominantly white (85%), college-educated (84%), married (69%) and employed (59%).
* Stage O or 1 (63%) or stage H or IHa (37%).
* Surgical recommendation included unilateral mastectomy or breast conservation therapy in 79% and bilateral mastectomy in 21%.
* Surgical treatment included: 49 with bilateral mastectomy (25%), 43 with unilateral mastectomy (22%), and 102 with breast conservation therapy (53%).
* Thirty-eight (23%) proceeded with surgery without testing results.
* Patients who carried the BRCA J/2 gene were more likely to undergo bilateral mastectomy (48%) than those with uninformative results (24%), or those who declined gene testing (4%) (j) < 0.001).
* Three factors were associated with the choice of bilateral mastectomy: positive gene test (odds ratio (OR) 3.53, 95% confidence interval (Cl) 1.43-8.69); recommendation for gene testing (OR 3.28, CI 1.34-8.03); and surgeon recommendation for bilateral mastectomy (OR 5.15, CI 2.21-12.03).
* Bivariate analysis of patients with uninformative gene testing and the choice of bilateral mastectomy was performed. Factors found to be associated with the choice of bilateral mastectomy included: the number of first degree relatives with breast or ovarian cancer; ethnic background other than Ashkcnazi Jewish; physician recommendation for GRCAJ/2 gene testing; and surgical recommendation to consider bilateral mastectomy.
Conclusions:
This large prospective study demonstrated that genetic counseling and testing of high-risk patients influences their surgical decision making. This study confirmed the findings of a previous small study. Not surprisingly physicians’ recommendations played a very important role in patients’ surgical decision-making.
Utilization of genetic counseling and testing should he offered to high-risk women with newly diagnosed breast cancer.
Selected references:
1. Weitzcl JN, McCaffrey SM, Ncdclcu R, it af. Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Arch Smg 2003; 138:1323-8
2. DcMarco TA, Peshkin RN, Brogan BM. Across the spectrum: case studies in genetic counseling for breast and ovarian cancer. J Genet Cotm; 2001;19:379-95
3. Schwartz MD, Peshkin BN, Hughes C, et al. Impact of RRCAJ/ GRCA2 mutation testing on psychologic distress in a clinic-bused sample. J CUn Onco! 2002;20:514-20
Commentary:
The risk of breast or ovarian cancer is high among those who carry a mutation of the BRCAJ or BRCA2 gene. Uene mutation carriers’ lifetime risk of breast cancer is 80% and their lifetime risk of ovarian cancer is 50% for BRCAJ and 20% for BRCA2 mutation carriers. Women with newly diagnosed breast cancer who are gene carriers also have an approximate 40% risk of the development of contralateral breast cancer at 10 years.
The role of genetic counseling and testing is to provide these women who carry the gene mutation with options to decrease their risk of developing breast or ovarian cancer. Bilateral mastectomy has been shown to decrease the risk of breast cancer by at least 90% and this risk reduction is improved if a woman also undergoes bilateral oophorectomy. Bilateral oophorectomy alone reduces the risk of breast cancer development in BRCAJ or BRCA2 gene carriers by approximately 50%. A similar reduction in contralateral breast cancer is seen in women, who are diagnosed with unilateral breast cancer and carry the gene mutation. Bilateral oophorectomy also prevents the development of ovarian cancer, leaving the patient with a residual 4% chance of developing primary peritoneal cancer. The use of tamoxifen as a prevention strategy has not shown consistent results in women with gene mutations.
A recent European trial examined the use of BRCAl and BRCA2 testing in a series of 192 women who were already diagnosed with breast and/or ovarian cancer and who came from high-risk families in which a BRCAl or BRCA2 mutation was eventually identified. Most of these women underwent genetic counseling after the initial treatment for their cancer. In this group, 35% requested bilateral or contralateral mastectomy and 49% requested oophorectomy. Women younger than 50 years of age and those who developed their first tumor after the initial identification of a BRCAl or BRCA2 mutation were more likely to undergo prophylactic surgery (p = 0.01). This trial confirms the desire for preventative surgery among this patient population who carry the gene mutation. Unfortunately, the study by Schwartz et al. reviewed the above did not comment on the discussion or use of prophylactic bilateral oophorectomy as a prevention strategy in their study patients.
Even though the prognosis of the first cancer in patients with BRCAl or BRCA2 mutations may dominate, interventions to prevent second primary cancers should be considered. At present we do not know if these preventive measures achieve increases in life expectancy in these women, but they may impact on the woman’s overall quality of life by lowering fear of a second cancer. It is general practice at our institution that all women who are at high- risk of carrying the BRCAl or BRCA2 mutation are offered genetic counseling and testing prior to any interventions. I feel that it is the surgical oncologist’s responsibility to identify these women and offer them all the treatment options, including surgical prevention.
Further reading:
Meijers-Hcijboer H, Brekelmans CTM, Menk-Pluymers M, et al. Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCAl or BRCA2 mutation. J Clin Oncol 21:1675-81
King M, Marks JH, Mandell JB, et al. Breast and ovarian cancer risks due to inherited mutations in BRCAl and BRCA2. Science 2003;302:643-64
Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: The PROSE Study Group. J Clin Oncol 2004;22:1055-62
Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCiAl and BRCA2 mutation carriers. J Clin Oncol 2004:22:2328-35
Schwarte MD, Lerman C, Brogan B, Peshkin BN, Hughes Halbcrt C, DeMarco T, Lawrence W, Main D, Finch C, Magnant C, Pennanen M, Tsangaris T, Willey S, Isaacs C. J Clin Oncol 2004:22:1823-9
Commentary by: Barbara A. Pockaj, MD, Department of Surgery, Mayo Clinic Scottsdale, Scottsdale, AZ 85259, USA
Copyright CRC Press Sep 2004