Interventions to improve psychosocial well-being in women with a BRCA mutation following risk-reducing surgery

Background
Women who test positive for a fault (mutation) on one of the BRCA genes (BRCA1 DNA repair associated or BRCA2 DNA repair associated (BRCA1 or BRCA2)) are more at risk of developing breast and tubo-ovarian cancer (cancer of the fallopian tubes or ovaries). A significant number of female BRCA carriers will choose to have surgery to remove their breast tissue and fallopian tubes and ovaries in order to reduce their risk of developing breast cancer and tubo-ovarian cancer. This type of surgery can be life-changing, and women may experience negative physical and emotional changes as a result. These changes can affect the function and appearance of their bodies, which in turn can have a negative psychological effect on women and their relationships.

Review question
The aim of this review was to learn if interventions can help with the social and psychological effects of physical and emotional changes in women who have had risk-reducing surgery.

Main findings
We found two studies that examined a psychosocial intervention for women who had undergone removal of their fallopian tubes and ovaries to reduce their risk of tubo-ovarian cancer.

One randomised controlled trial (a study in which participants are assigned to one of two or more treatment groups using a random method) assessed a mindfulness-based stress reduction training programme for menopausal symptoms after risk-reducing surgery. Whilst there was improvement in the menopause-specific quality of life scores in the short and the long term for women with menopausal symptoms, the intervention was not associated an with improvement in sexual functioning or distress.

Women who participated in a non-randomised study all received the study intervention and scored themselves on certain items related to psychosexual functioning and psychological adjustment before and after the intervention (targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies). They also received a group psychoeducation session and telephone counselling. The outcomes were based on the differences between the before and after scores. All women recruited to the study were at risk of tubo-ovarian cancer based on having a harmful or faulty BRCA gene, but there was no personal history of tubo-ovarian cancer in the group studied.

No studies reported on social and psychological interventions following risk-reducing surgery to have breast tissue removed in BRCA carriers.

Quality of the evidence
The certainty (quality) of the evidence ranged from moderate to very low, with only one randomised controlled trial and one non-randomised study that had no comparator included in the review. Both studies involved small numbers of women.

Conclusions
The limited, moderate- to very low-certainty evidence meant that we were unable to draw any conclusions regarding psychosocial interventions following risk-reducing surgery in female BRCA carriers on improvement in quality of life and psychological (emotional) adjustment. Further research is required to determine how best to support women who choose to have risk-reducing surgery.

Authors' conclusions: 

The effect of psychosocial interventions on quality of life and emotional well-being in female BRCA carriers who undergo risk-reducing surgery is uncertain given the very low methodological quality in the two studies included in the review. The absence of such interventions highlights the need for partnership between researchers and clinicians in this specific area to take forward the patient-reported outcomes and develop interventions to address the psychosocial issues related to risk-reducing surgery in female BRCA carriers, particularly in this new era of genomics, where testing may become more mainstream and many more women are identified as gene carriers.

Read the full abstract...
Background: 

Women who carry a pathogenic mutation in either a BRCA1 DNA repair associated or BRCA2 DNA repair associated (BRCA1 or BRCA2) gene have a high lifetime risk of developing breast and tubo-ovarian cancer. To manage this risk women may choose to undergo risk-reducing surgery to remove breast tissue, ovaries, and fallopian tubes. Surgery should increase survival, but can impact women's lives adversely at the psychological and psychosexual levels. Interventions to facilitate psychological adjustment and improve quality of life post risk-reducing surgery are needed.

Objectives: 

To examine psychosocial interventions in female BRCA carriers who have undergone risk-reducing surgery and to evaluate the effectiveness of such interventions on psychological adjustment and quality of life.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE and Embase via Ovid, CINAHL, PsycINFO, Web of Science up to April 2019 and Scopus up to January 2018. We also handsearched abstracts of scientific meetings and other relevant publications.

Selection criteria: 

We included randomised controlled trials (RCT), non-randomised studies (NRS), prospective and retrospective cohort studies and interventional studies using baseline and postintervention analyses in female BRCA carriers who have undergone risk-reducing surgery.

Data collection and analysis: 

Two review authors independently assessed eligibility studies for inclusion in the review. We used standard methodological procedures expected by Cochrane.

Main results: 

We screened 4956 records from the searches, selecting 34 unique studies for full-text scrutiny, of which two met the inclusion criteria: one RCT and one NRS. The included studies assessed 113 female BRCA carriers who had risk-reducing surgery, but there was attrition, and outcome data were not available for all participants at final study assessments. We assessed the RCT as at a high risk of bias whilst the NRS did not have a control group. Our GRADE assessment of the studies was very low-certainty due to the paucity of data and methodological shortcomings of the studies. The primary outcome of quality of life was only measured in the RCT and that was specific to the menopause. Both studies reported on psychological distress and sexual function. Neither study measured body image, perhaps because this is most often associated with risk-reducing mastectomy rather than oophorectomy.

The RCT (66 participants recruited with 48 followed to 12 months) assessed the short- and long-term effects of an eight-week mindfulness-based stress reduction (MBSR) training programme on quality of life, sexual functioning, and sexual distress in female BRCA carriers (n = 34) in a specialised family cancer clinic in the Netherlands compared to female BRCA carriers (n = 32) who received usual care. Measurements on the Menopause-Specific Quality of Life Questionnaire (MENQOL) showed some improvement at 3 and 12 months compared to the usual care group. At 3 months the mean MENQOL scores were 3.5 (95% confidence interval (CI) 3.0 to 3.9) and 3.8 (95% CI 3.3 to 4.2) for the MBSR and usual care groups respectively, whilst at 12 months the corresponding values were 3.6 (95% CI 3.1 to 4.0) and 3.9 (95% CI 3.5 to 4.4) (1 study; 48 participants followed up at 12 months). However, these results should be interpreted with caution due to the very low-certainty of the evidence, where a lower score is better. Other outcome measures on the Female Sexual Function Index and the Female Sexual Distress Scale showed no significant differences between the two groups. Our GRADE assessment of the evidence was very low-certainty due to the lack of blinding of participants and personnel, attrition bias and self-selection (as only one-third of eligible women chose to participate in the study) and serious imprecision due to the small sample size and wide 95% CI.

The NRS comprised 37 female BRCA carriers selected from three Boston-area hospitals who had undergone a novel sexual health intervention following risk-reducing salpingo-oophorectomy (RRSO) without a history of tubo-ovarian cancer. The intervention consisted of targeted sexual-health education, body awareness and relaxation training, and mindfulness-based cognitive therapy strategies, followed by two sessions of tailored telephone counselling. This was a single-arm study without a control group. Our GRADE assessment of the evidence was very low-certainty, and as there was no comparison group in the included study, we could not estimate a relative effect. The study reported change in psychosexual adjustment from baseline to postintervention (median 2.3 months) using measures of Female Sexual Function Index (n = 34), which yielded change with a mean of 3.91, standard deviation (SD) 9.12, P = 0.018 (1 study, 34 participants; very low-certainty evidence). The Brief Symptom Inventory, Global Severity Index yielded a mean change of 3.92, SD 5.94, P < 0.001. The Sexual Self-Efficacy Scale yielded change with a mean of 12.14, SD 20.56, P < 0.001. The Sexual Knowledge Scale reported mean change of 1.08, SD 1.50, P < 0.001 (n = 36). Participant satisfaction was measured by questionnaire, and 100% participants reported that they enjoyed taking part in the psychoeducation group and felt "certain" or "very certain" that they had learned new skills to help them cope with the sexual side effects of RRSO.