Behavioral and psychosocial effects of rapid genetic counseling and testing in newly diagnosed breast cancer patients: a multicenter study

In the Netherlands, breast cancer is the most common form of cancer.
Approximately 12,000 women are diagnosed annually, of whom about 5-10% carry a
mutation in a breast cancer gene. Genetic counseling and DNA testing are
usually offered to selected patients after primary treatment has been completed
(e.g. the first year after diagnosis). For women with a mutation in one of the
two breast-ovarian cancer syndrome genes, BRCA1 and BRCA2, chances of a second
breast cancer are high, and therefore a proportion of these women may opt for
preventive measures in addition to their immediate breast cancer treatment.
Contralateral prophylactic mastectomy significantly reduces this risk, and is
associated with a reduction in mortality. Genetic counseling and testing for
breast cancer typically takes approximately 4-6 months to complete. However,
some hospitals and laboratories are now able to generate test results within 3
to 6 weeks. This technology of rapid genetic testing creates new opportunities
for providing both women and their treating surgeons with information
potentially relevant for deciding between available treatment options,
including type of surgery and adjuvant therapy. It is expected that women with
a BRCA gene mutation more often will opt for a bilateral mastectomy. However,
research is needed to determine if this hypothesis is correct. Additionally,
few data are as yet available on the treatment-related and psychosocial
consequences of genetic testing and risk-reducing behavior among individuals
with a recent diagnosis of breast cancer.

The proposed study will focus on newly diagnosed breast cancer patients who,
prior to receiving treatment, are identified on the basis of age or family
history of breast or ovarian cancer as having at least a 10% risk of carrying a
mutation in the BRCA1 or BRCA2 genes. We will investigate whether women with a
recent diagnosis of breast cancer make use of rapid genetic counseling when
offered. Furthermore, we will investigate whether the process of genetic
counseling (and subsequent DNA testing) has influence on the choice of
treatment, and whether and how such rapid genetic counseling and testing (RGCT)
affects levels of risk perception, cancer-related worries and distress, and
decisional satisfaction.

This multicenter study will employ a randomized controlled trial. In an 18
month period newly diagnosed breast cancer patients will be recruited from 13
hospitals in the Amsterdam and Utrecht regions of the Netherlands. Eligible
patients will be randomized either to the *usual care* (UC) arm of the study,
or to the RGCT arm of the study. The randomization will be done in a ratio of
1:2, leading to 85 patients in the UC arm and 170 patients in the RGCT arm.

Women in the RGCT arm of the study will be referred for genetic counseling
within a week after diagnosis, prior to the primary surgery. Genetic counseling
will take place at the NKI-AVL or the UMC Utrecht, If a DNA-test is indicated,
a blood sample for this test can be provided by the patient on the same day. If
necessary, the results will be known within 3 to 6 weeks.

Women in the UC condition will receive standard advice and care from their
treating physician. In some cases, patients may be referred by the treating
surgeon or self-refer to genetic counseling. However, in current practice, this
occurs rarely during the pre-surgery period.

Standardized questionnaires will be administered to all patients at study
entry, and at 6 and 12 months to assess all psychosocial outcomes. The study
endpoints will include: (1) the choice of clinical management strategy,
including the uptake of direct bilateral mastectomy (BLM) or of delayed
preventive contralateral mastectomy (PCM); (2) cancer risk perception,
cancer-related worry and distress; (3) knowledge of genetic aspects of breast
cancer; (4) decisional satisfaction; and (5) health-related quality of life
(HRQL).The study will also evaluate women*s experience of and satisfaction with
RGCT (i.e., the timing and quality of the services provided, the perceived
impact on treatment decisions, perceived need for additional psychosocial
services, etc.). Data on surgical outcomes will be abstracted from the medical
records. A subset of women will be interviewed to obtain supplementary,
qualitative data about the RGCT experience.

During 18 months about 2550 women in the regions of Amsterdam and Utrecht will
be diagnosed with breast cancer. Based on previous research, the estimated
number of women with a probable hereditary form of breast cancer is 400. We
expect that 255 of these women will participate in the study.

Women in the RGCT arm of the study will be referred for genetic counseling
within a week after diagnosis, prior to the primary surgery. Genetic counseling
will take place at the NKI-AVL or the UMC Utrecht, If a DNA-test is indicated,
a blood sample for this test can be provided by the patient on the same day. If
necessary, the results will be known within 3 to 6 weeks.

Answering the questionnaires will take about 45-60 minutes each time.
For some people answering questions about their health and cancer risks, might
be a burden.
The information given during genetic counseling might be a burden.