Article Text

Original research
Surgical decision making in premenopausal BRCA carriers considering risk-reducing early salpingectomy or salpingo-oophorectomy: a qualitative study
  1. Faiza Gaba1,2,
  2. Shivam Goyal3,
  3. Dalya Marks4,
  4. Dhivya Chandrasekaran1,2,
  5. Olivia Evans1,2,
  6. Sadiyah Robbani5,
  7. Charlotte Tyson5,
  8. Rosa Legood6,
  9. Ertan Saridogan7,
  10. W Glenn McCluggage8,
  11. Helen Hanson9,
  12. Naveena Singh10,
  13. D Gareth Evans11,
  14. Usha Menon12,
  15. Ranjit Manchanda3,13
  16. on behalf of the PROTECTOR team
    1. 1Wolfson Institute of Preventive Medicine, Barts CRUK Centre, Queen Mary University of London—Charterhouse Square Campus, London, UK
    2. 2Gynaecological Oncology, Barts Health NHS Trust, London, UK
    3. 3Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK
    4. 4Department of Public Health, Environments and Society, Faculty of Public Health and Policy, London School of Hygiene & Tropical Medicine, London, UK
    5. 5Centre for Experimental Cancer Medicine, Barts CRUK Cancer Centre, Queen Mary University of London, London, UK
    6. 6Health Services Research and Policy, London School of Hygiene and Tropical Medicine, London, UK
    7. 7Department of Gynaecology, University College London Hospitals NHS Foundation Trust, London, UK
    8. 8Department of Pathology, Belfast Health and Social Care Trust, Belfast, UK
    9. 9South West Thames Regional Genetics Service, South West Thames Regional Genetic Services, London, UK
    10. 10Department of Pathology, Barts Health NHS Trust, London, UK
    11. 11Centre for Genomic Medicine, University of Manchester, Manchester, UK
    12. 12MRC Clinical Trials Unit, University College London, London, UK
    13. 13Department of Gynaecological Oncology, Barts Health NHS Trust, London, UK
    1. Correspondence to Professor Ranjit Manchanda, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London EC1M 6BQ, UK; r.manchanda{at}qmul.ac.uk

    Abstract

    Background Acceptance of the role of the fallopian tube in ‘ovarian’ carcinogenesis and the detrimental sequelae of surgical menopause in premenopausal women following risk-reducing salpingo-oophorectomy (RRSO) has resulted in risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) being proposed as an attractive alternative risk-reducing strategy in women who decline/delay oophorectomy. We present the results of a qualitative study evaluating the decision-making process among BRCA carriers considering prophylactic surgeries (RRSO/RRESDO) as part of the multicentre PROTECTOR trial (ISRCTN:25173360).

    Methods In-depth semistructured 1:1 interviews conducted using a predeveloped topic-guide (development informed by literature review and expert consultation) until informational saturation reached. Wording and sequencing of questions were left open with probes used to elicit additional information. All interviews were audio-recorded, transcribed verbatim, transcripts analysed using an inductive theoretical framework and data managed using NVIVO-v12.

    Results Informational saturation was reached following 24 interviews. Seven interconnected themes integral to surgical decision making were identified: fertility/menopause/cancer risk reduction/surgical choices/surgical complications/sequence of ovarian-and-breast prophylactic surgeries/support/satisfaction. Women for whom maximising ovarian cancer risk reduction was relatively more important than early menopause/quality-of-life preferred RRSO, whereas those more concerned about detrimental impact of menopause chose RRESDO. Women managed in specialist familial cancer clinic settings compared with non-specialist settings felt they received better quality care, improved hormone replacement therapy access and were more satisfied.

    Conclusion Multiple contextual factors (medical, physical, psychological, social) influence timing of risk-reducing surgeries. RRESDO offers women delaying/declining premenopausal oophorectomy, particularly those concerned about menopausal effects, a degree of ovarian cancer risk reduction while avoiding early menopause. Care of high-risk women should be centralised to centres with specialist familial gynaecological cancer risk management services to provide a better-quality, streamlined, holistic multidisciplinary approach.

    • surgical oncology
    • gynecology
    • genetics
    http://creativecommons.org/licenses/by-nc/4.0/

    This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

    Statistics from Altmetric.com

    Introduction

    BRCA1/BRCA2 mutation carriers have a ~70% lifetime risk of breast cancer (BC) and ~17%–44% lifetime risk of ovarian cancer (OC).1 RAD51C/RAD51D/BRIP1/PALB2 are newer moderate penetrance OC genes, whose risks were recently validated (5%–13% lifetime cumulative OC risk) with RAD51C/RAD51D/PALB2 also associated with increased BC risk (20%–53%).2 3 BC risk management options include annual (eg, MRI) breast screening;4 chemoprevention (eg, Tamoxifen/Anastrazole))5 6 and surgical prevention (risk-reducing mastectomy (RRM)).7 Risk-reducing salpingo-oophorectomy (RRSO), usually recommended from 35 to 40 years, is the most effective surgical prevention option for OC-risk reduction, especially given the absence of an effective national (or even approved) high-risk OC-screening programme. However, premenopausal RRSO leads to early surgical menopause which has detrimental long-term health sequelae (increased risk of coronary heart disease, osteoporosis, vasomotor symptoms, sexual dysfunction, neurocognitive decline) particularly in women unable to use hormone replacement therapy (HRT).8–13 Widespread acceptance of a central role for the fallopian tube in the development of high-grade serous carcinoma (HGSC), the most common type of OC has led to early salpingectomy (ES) followed by delayed oophorectomy (DO) proposed as an attractive alternative two-step OC surgical prevention strategy in premenopausal women who have completed their family but decline/wish to delay RRSO. Epidemiological studies show 70% of occult lesions identified in high-risk women undergoing RRSO occur in the tube and that salpingectomy may reduce ovarian cancer risk in low-risk women by 42%–65%. Thus, it is anticipated that risk-reducing early-salpingectomy with delayed oophorectomy (RRESDO) will provide some level of risk reduction while conserving ovarian function to avoid the negative impact of early menopause.

    Three trials in the UK (PROTECTOR), Netherlands (TUBA) and US (WISP) are currently offering RRESDO within a controlled research setting. Absence of prospective data strengthens offering RRESDO currently solely within a research setting. The precise estimate of OC risk reduction and the long-term health outcomes associated with ES remain unclear. Salpingectomy will not prevent OC arising outside the tube. Residual fimbrial tissue (most HGSC arise from tubal fimbria) may remain implanted on the ovarian surface postsalpingectomy in 9.8% cases14 and represents a possible site of malignant transformation. The natural history of different types of serous-tubal intraepithelial carcinoma (STIC), the precursor of tubal HGSC and rate-limiting step in OC development remain unknown.15 STICs may not be precursors to all OC.16 The long-term impact of salpingectomy on sexual function, endocrine function and menopause onset is unknown. Concerns remain regarding attrition from DO and uncertainties persist around cost effectiveness.17

    There is a paucity of qualitative data on the decision-making process for RRESDO in BRCA carriers.18 Limited data suggest that the seriousness of OC, family history (FH), previous BC, uncertainty around effect of ES and ease of decision to undergo RRSO are barriers to undergoing RRESDO.18 The main facilitator is longer preservation of ovarian function.18 RRESDO appears acceptable particularly to women concerned about sexual dysfunction.19 Barriers to RRSO include early menopause, sexual dysfunction and loss of fertility; facilitators include FH, fear of dying, concurrent benign gynaecological issues, ineffective screening and physician recommendation.18 20–22

    Current medical decision making encourages clinicians to respect patients’ preferences and be guided by them for treatment decisions.23 Policy makers and commissioners increasingly use qualitative data to inform guideline development and care pathways, as it enables care provision according to user insights by gaining a better understanding of, and reasons for the choices made. We report on the decision making of high-risk UK women undergoing/considering prophylactic surgery in the PROTECTOR trial (ISRCTN 25173360). This study aims to evaluate the decision-making process among BRCA carriers considering prophylactic surgeries. We offer novel insights for healthcare professionals providing decision support to BRCA carriers and for development of clinical management pathways for these women.

    Methods

    Study design

    Qualitative substudy nested within a multicentre, observational cohort trial (PROTECTOR: Preventing Ovarian Cancer through early Excision of Tubes and late Ovarian Removal, ISRCTN:25173360) with three arms: RRESDO; RRSO; no surgery.24 Premenopausal women (follicle stimulating hormone (FSH) levels<40), >30 years, at increased risk of OC (BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 carriers or due to a strong family history) were recruited to the PROTECTOR trial (www.protector.org.uk) through specialist high-risk familial cancer clinics (FCC), genetics, gynaecology/gynaecological oncology clinics. Exclusion criteria included being postmenopausal, previous bilateral salpingectomy or bilateral oophorectomy, pregnancy, future plan of childbearing (surgical arms only), prior OC/peritoneal malignancy, <12 months from cancer treatment, OC suspicion at baseline. Participants self-selected their chosen study arm following informed counselling.

    In-depth semistructured one-to-one telephone interviews were conducted (by FG) using a predeveloped topic-guide (online supplemental material 1). Topic-guide development was informed by a literature review and expert consultation. Wording and sequencing of questions were left open with probes used to elicit more information as appropriate. Questions were refined following a pilot interview, and topics covered included: background (family structure, support network, occupation, hobbies); risk-reducing surgery for OC/BC prevention; health values; satisfaction-and-regret. Following informed consent, interviewees were recruited based on sociodemographics (age, ethnicity, marital status, postcode), parity, BC history, trial arm (RRESDO, RRSO, no surgery) and ascertainment location (high-risk FCC, gynaecology clinic, gynaecological oncology clinic, genetics clinic) to ensure adequate representation across the PROTECTOR cohort. Field notes were made, interviews audio-recorded and transcribed verbatim. Interviews were conducted (before OC prevention surgery) between November 2018 and October 2019 until data saturation was reached.

    Data analysis

    Transcripts were analysed using a grounded-theory approach and data managed using NVIVO V.12 software. The analysis aimed to directly reflect the views and experiences of participants’ and not those predetermined by the researchers. Two researchers (FG, SG) independently coded all transcripts, following a three-step process: open coding, axial coding and selective coding. Meaningful text was labelled starting with a line-by-line analysis (open coding). Open codes were categorised, grouping similar codes, refined and combined into larger themes (axial coding). Through multiple, iterative discussions, we reflected on potential relationships between codes within and across cases and developed an in-depth understanding of themes. Coding disagreements were resolved through discussion with further transcript review until reaching consensus. Transcripts were re-reviewed to ensure themes reflected the data and important ideas/views had not been missed/over-represented. Selective coding involved integrating and refining themes. Analysis was performed in parallel with data collection and finalised once theoretical saturation was reached.

    Results

    Participant characteristics

    Twenty-four women were interviewed, with no interview refusals. Participant characteristics are summarised in table 1. Participants ranged from 34 to 46 years; 22 were Caucasian, 19 married, 4 nulliparous, 4 had previously BC themselves, 9 had undergone RRM, 14 were BRCA1 carriers, 10 BRCA2 carriers, 11 self-selected RRESDO, 7 RRSO and 6 no surgery. Interviews lasted 40–70 (mean=55) min.

    Table 1

    Participant characteristics

    Themes

    Seven themes pertinent to decision making emerged: fertility; menopause; cancer risk reduction: surgical choices; surgical complications; sequence of ovarian and breast prophylactic surgeries; support with decision making; satisfaction with treatment choices. Table 2 summarises the facilitators and table 3 the barriers per-theme and surgical prevention strategy. Figure 1 maps the decision-making options for premenopausal BRCA carriers considering risk-reducing surgery.

    Figure 1

    Decision making aid for premenopausal BRCA carriers considering risk reducing surgery. BC, breast cancer; HRT, hormone replacement therapy; OC, ovarian cancer; RRESDO, risk reducing early salpingectomy with delayed oophorectomy; RRM, risk reducing mastectomy; RRSO, risk reducing salpingo-oophorectomy.

    Table 2

    Thematised facilitators to uptake of risk reducing surgeries

    Table 3

    Thematised barriers to uptake of risk reducing surgeries

    Fertility

    ID-03 (RRESDO-arm): ‘I just think because I know that I’ve completed my family and I don’t want these old tubes anymore anyway, I just see it [surgery] as being something positive that I can do for myself, to hopefully reduce my risk of cancer.’

    Fertility was an important consideration for all women. For 18 women choosing surgery (RRESDO/RRSO), 16 completed childbearing and two didn’t want children. Once fertility was not a barrier, deciding to undergo surgery was less complex and a natural next step. Four women had not completed childbearing, wished to delay surgery and joined the control arm. Two control arm women despite completing childbearing delayed surgery. One was undecided what to choose and the second had strong beliefs against removing healthy tissue and any risk-reducing surgery.

    Two women opted to conceive through in vitro fertilisation (IVF) and preimplantation genetic diagnosis (PGD). Both acknowledged PGD/IVF was physically and mentally stressful with multiple hospital visits and additional procedures but considered it an acceptable tradeoff to prevent their children being BRCA carriers and facing similar difficult decisions. One participant felt she may have not proceeded with a natural conception if IVF/PGD had failed.

    Menopause

    ID-06 (RRESDO-arm): ‘I wasn’t happy with the impact of going in to menopause straight away and although you obviously have HRT options which might be offered if you go to a good gynaecologist, I just, I wasn’t convinced that HRT brings you back up to an even keel or level, the way that I’m feeling right now which is basically very balanced.’

    Interviewees who chose RRESDO (n=11) did so because of concerns about detrimental consequences of early menopause following oophorectomy, particularly low mood, sexual dysfunction and poorer QoL. All RRESDO interviewees found the uncertainty regarding long-term health implications (eg, possibility of earlier menopause following ES) an acceptable risk. Interviewees rationalised RRESDO as a preferential strategy to delay early menopause and its long-term consequences while benefiting from some OC risk reduction. Two women would have delayed risk-reducing surgery until they were near/at natural menopause if RRESDO was unavailable, whereas another would have undergone RRSO instead. Two RRESDO women found avoiding need for HRT and repeat prescription costs more appealing. RRESDO interviewees wanted to be in control of choosing the timing of DO (with their clinician) and felt a fixed timing for DO was a barrier to RRESDO uptake. Menopause was a lesser concern to older premenopausal women (nearer the age of natural menopause) self-selecting RRSO because RRESDO would only delay menopause by a few years and require an additional operation.

    RRSO women managed outside specialist high-risk clinics reported receiving conflicting advice on HRT safety, lack of information on HRT efficacy for symptom relief and struggling with HRT access. A number of gynaecologists/gynaecological oncologists do not routinely counsel women about health consequences of early menopause, lack awareness of HRT safety and do not offer HRT to BRCA carriers undergoing premenopausal RRSO (particularly those near natural menopause age). Women attending BRCA support forums felt unsupported without follow-up after surgery and reported persistent menopausal symptoms detrimentally affecting QoL despite HRT. Women managed within a high-risk FCC reported being more reassured with their planned follow-up and access to a menopause specialist post-RRSO.

    Cancer risk reduction: surgical choices

    Ovarian-cancer risk-reducing surgery

    ID-08 (RRESDO-arm): ‘It’s [RRESDO] acceptable because it’s my decision making as well, it’s not at the fault of any health professional, no-one is making me do it this way, it’s my decision and I'm aware of that.’

    Women who prioritised avoiding menopause and preserving QoL selected RRESDO. While, women concerned about the precision of risk reduction and who prioritised maximising OC risk reduction, selected RRSO. Women with a strong FH of OC selected RRSO, and with strong FH of BC preferred RRESDO.

    RRESDO interviewees felt comfortable and empowered with the tradeoff between an uncertain degree of OC risk reduction and avoidance of early menopause. They rationalised they were doing ‘…something to reduce risk as opposed to nothing…’ while avoiding early menopause and preserving their QoL.

    A few interviewees reported being counselled/reading they were at increased endometrial cancer risk and were offered/requested a concomitant hysterectomy.

    Breast-cancer risk-reducing surgery

    ID-01 (No-surgery-arm): ‘…it’s also quite difficult to decide to go through a major operation when there’s nothing wrong, so obviously it’s preventative but part of you is like “I'm perfectly healthy, why would I do this?”, and there’s something quite emotional about the idea of having your breast removed as well, whereas the ovaries aren’t seen, it’s about appearance as well and just having implants and things like that.’

    Interviewees considered RRM decision making much harder compared with RRSO/RRESDO. Women were conflicted with wanting to optimise BC prevention while preserving breasts for femininity and self-esteem. They preferred delaying RRM until finishing childbearing and breastfeeding.

    ID-13 (RRSO-arm): ‘I never went away thinking, “I've got the all clear”, I went away feeling like, “As far as anyone can tell I've got the all clear”, and then the anxiety would start to rise again as we headed towards the next five month mark point when I could see it looming in the diary.’

    Some women reported anxiety/stress with breast s

    Nine women underwent RRM and five struggled with decision making on reconstruction with flaps or implants; and consideration of nipple-sparing versus non-nipple-sparing surgeries. Two highlighted lack of healthcare professional support for women opting against reconstruction. One interviewee regretted her decision of flap reconstruction due to resultant cosmetic appearance and chronic pain but did not regret RRM.

    All BC-affected interviewees selected OC-prevention surgery purely for preventing OC. They felt alternative treatments were available to improve BC survival. Women selecting RRESDO did not consider the potential loss of improved BC-survival from oophorectomy a barrier.

    Surgical complications

    ID-18 (RRESDO-arm): ‘…the trade-off between having two surgeries as opposed to one, that does feel absolutely fine to me, and that’s maybe because I've had positive experiences with surgery before.’

    Women with previous positive surgical experiences (good relationship with surgeon, postoperative care, no complications) and/or good health found two-staged RRESDO acceptable, without concerns for increased surgical complications or hospital appointments. Inspection of pelvis/abdomen for OC at RRES was reassuring for one patient. One RRSO interviewee highlighted concerns of two surgeries as future health may deteriorate with age and increase risks of surgical complications.

    Sequence of ovarian and breast prophylactic surgeries

    Sequential surgery

    ID-16 (RRESDO-arm): ‘Because I’ve never had an operation, I thought it would be better to have a minor operation first, just to kind of prepare me rather than going straight into major surgery, that was one reason but the other was the ovarian cancer prevention felt more pressing because I'm on the breast screening programme and it didn’t feel quite so urgent.’

    Interviewees reported preferring OC prevention surgery before RRM because of lack of an OC screening programme; poorer prognosis of OC; being a laparoscopic procedure with quick recovery; inability to self-examine ovaries. Women with a stronger FH of OC preferred RRSO first and those with a FH of BC chose undergoing RRM first. Sequence was also dependent on surgical referral and appointment times with some experiencing shorter waiting times for seeing a breast surgeon than a gynaecologist/gynaecological oncologist.

    Combined ovarian and breast prophylactic surgery

    ID-11 (RRESDO-arm): ‘Just throw everything at it, and let’s just get it all sorted in one.’

    Fifteen women would have preferred a single combined risk-reducing procedure involving RRM±reconstruction along with OC preventative surgery. Reasons included fewer surgeries, less anxiety, less waiting, fewer appointments, less time off work and single surgical recovery. However, nine women expressed concerns over possible increased recovery time and increased psychological distress from early menopause impacted by RRM associated body image issues.

    Support with decision making

    Clinical support

    ID-05 (RRESDO-arm): ‘…my experience of [gynaecology] appointments is that people just present things to you, and very quickly you have to make a decision, and there isn’t a way to just, some of the decisions take a lot of discussion, and coming back to it, and rethinking, and I just feel that there isn’t that space for it…’

    Interviewees expressed preference for multiple appointments with gynaecologists/gynaecological oncologists for discussing risk-reducing surgery. Decision making was a complex/dynamic process, with one visit being inadequate to absorb/assimilate complex information, and make an informed decision. Interviewees felt more supported with RRM decision making, given access to a psychologist and multiple breast surgical appointments before RRM. Interviewees wished to be routinely offered an ‘optional’ (not compulsory) consultation with a psychologist prior to OC preventative surgery.

    Interviewees who had done personal research (reading literature, speaking to BRCA carriers, online support groups (OSGs)) felt their decision was validated following counselling from healthcare professionals. Counselling received aided decision making of women who had not done any personal research. Counselling lacked information on communicating genetic test results to children and complex decisions carriers faced.

    Patient support groups

    ID-05 (RRESDO-arm): ‘I know there are [online] forums, but a lot of it, there’s a lot of fearful ideas there, and my cousin was saying that she just had to stop going on those forums.’

    Continuous availability/access and anonymity were advantages of online BRCA support groups/forums reported by our cohort. However, interviewees also highlighted negative personal experiences (and anxiety) given poor surgical outcomes/negative experiences discussed at these outlets which were not balanced with positive outcomes. Interviewees used online forums for an ad-hoc-specific query rather than for regular support. Clinician-led educational days with experts’ talks about management options, opportunities to ask questions, share experiences and meet other BRCA carriers appeared preferable.

    Lifestyle support

    ID-22 (RRSO-arm): ‘When I realised that I’d have to go through with a number of operations to help reduce the risk, I made sure that I was in the best possible health beforehand to deal with those and I was really glad that I did.’

    RRESDO/RRSO women were eating healthier, losing weight and exercising regularly to minimise postoperative complications and shorten recovery time. Even no-surgery interviewees made healthier choices (smoking cessation, reduced alcohol, exercise, diet) to increase their conception chances.

    Satisfaction with treatment choices

    ID-16 (RRESDO-arm): ‘I'm at peace over the situation, and it’s not something that has caused me anxiety, although I don’t really like procedures and hospitals as I've said, but I feel that it’s something that I can manage.’

    Interviewees felt it difficult to state outright satisfaction with their decision to have/not have preventative surgery but rationalised their decision making. Women delaying surgery were concerned about developing cancer. Women undergoing surgery were also concerned about developing cancer along with surgical complications, impact on QoL and psychological health. However surgery reduced OC/BC anxiety.

    ID-18 (RRESDO-arm): ‘I’d done quite a bit of research myself. I found all of the people that I’ve met within the team have been fantastic and haven’t just treated me like Patient X who doesn’t know anything at all.’

    Interviewees managed within high-risk multidisciplinary FCC appeared more satisfied than those managed in genetics/gynaecology/gynaecological oncology clinics. Reasons included a more personalised approach, information tailored to the individual’s pre-existing knowledge base, same-day consultations with multiple specialists and continuity of care. The combination of specialists supporting FCCs varied but included: geneticists, gynaecologists, breast surgeons, menopause specialists, fertility specialists, psychologists. All seven women previously under the care of non-specialist clinics reported higher satisfaction levels when subsequently managed in the FCC setting.

    ID-13 (RRSO-arm): ‘…it does take time, like relieve yourself of that sense of pressure of having to come to a decision…’

    Interviewees would advise fellow BRCA carriers to avoid time-pressure with surgical decision making, talk to other BRCA carriers, do personal research, ask for second opinions if not satisfied.

    No-surgery interviewees would regret their decision to delay/avoid surgery if they developed OC. Women undergoing surgery would regret it if a life-changing surgical complication occurred.

    Discussion

    We identified seven interconnected themes integral to surgical prevention decision making in BRCA carriers. To the best of our knowledge, this is the first qualitative study that has mapped all aspects of the decision-making process of BRCA carriers undergoing/considering all ovarian (RRESDO/RRSO)/breast (RRM)/combined risk-reducing surgical options (figure 1). Women for whom maximising OC risk reduction was relatively more important than early menopause/QoL preferred RRSO, whereas those more concerned about impact of menopause chose RRESDO.

    While some facilitators/barriers we describe for RRESDO are similar to those reported earlier, we found some differences too.18 19 25 Unlike a Dutch study reporting a personal history of BC as a barrier, we report that BC-affected BRCA carriers found RRESDO acceptable despite potential for improved BC survival afforded by premenopausal oophorectomy. BC-affected and unaffected BRCA carriers selecting RRESDO were equally concerned about avoiding early menopause/maintaining QoL. This apparent difference in RRESDO acceptability among UK and Dutch women may be attributed to differences in counselling, risk-management options available, population differences, evolving scientific evidence base, its interpretation by clinicians and patients and changing practices. Oophorectomy may not reduce primary/contralateral BC risk26–29 and effective adjunct treatments to improve BC outcomes are available including contralateral mastectomy, GnRH analogues, selective estrogen receptor modulators etc.

    Approaching the age of natural menopause and concerns over future poor health were new barriers to RRESDO we elicited. Previously unreported RRESDO facilitators identified include avoiding the need for HRT and significant concerns about not adequately alleviating menopausal symptoms or improving QoL. This highlights women’s unease and apprehension related to effects of menopause.30 Premenopausal women concerned about sexual dysfunction are more likely to opt for RRESDO.19 Despite HRT, symptom levels following premenopausal oophorectomy, particularly for sexual dysfunction, remain above those retaining their ovaries.31 As part of RRSO decision making all premenopausal women should be involved in formulating an individualised presurgical HRT plan and fully counselled on menopausal issues along with the benefits and limitations of HRT.

    Other RRESDO facilitators we identified include positive experience with previous surgery, reducing the anxiety of doing nothing and flexible timing of DO. The Dutch-TUBA,32 and US-PSDO (Prophylactic Salpingectomy with Delayed Oophorectomy)33 studies undertake DO well before onset of menopause (without the option to delay until natural menopause). This could have been a barrier for UK women. However, in the UK PROTECTOR, and US WISP (Women Choosing Surgical Prevention)6 trials, women can choose when to undergo DO but are encouraged to do this by natural menopause. The facilitator and barriers to RRSO/RRM elicited in our cohort are similar to those reported earlier.22 33–37

    We too found undergoing preventative surgery reduced anxiety.18 34 35 Although RRM decision making was more complex than OC preventative surgery, women felt more supported in their decision to undergo RRM (than OC prevention) due to psychology input and multiple breast surgical appointments. This reflects the well-established tertiary care BC risk-management pathways in the UK.38 We found disparities in OC risk management care across the UK. Women managed in high-risk FCC settings were more satisfied with their care and received better support and HRT access. The lower satisfaction in women managed in non-specialist clinics was linked to non-streamlined clinical pathways, need for multiple referrals, delays in seeing different specialists, lack of continuity of care and difficulties in assimilating large volumes of information in a single appointment. Others too have reported low satisfaction with poorly developed care pathways.36 39 Of particular concern was poor HRT counselling and management, also reported previously.20 High-risk women need to be supported by a multidisciplinary team comprising geneticists, gynaecologists/gynae-oncologists with a special interest, breast oncologists, oncoplastic surgeons, menopause specialists, fertility specialists, psychologists and specialist nurses. Our findings support centralising care of high-risk women to centres which have specialist high-risk multidisciplinary FCC services and the need to develop more such services/centres with well-defined care pathways.

    Our data suggest that women engage concurrently in both OC and BC prevention decision making in contrast to some studies suggesting that women prioritise decisions and make them one at a time.36 40 41 We identified a demand for combined OC-and-BC prevention surgery. However, only few centres currently offer this, the psychological/QoL effects following combined BC/OC prophylactic surgery are unknown and not all women may be suitable candidates. Combined surgery offers logistical practicality for busy working women with dependent families by limiting the hospital appointments/surgeries/postoperative recoveries and has high satisfaction.40 Initial data suggest that a combined approach has lower costs than separate procedures40 but formal cost-utility analysis including sensitivity analysis is needed. Additionally, RRESDO may be more acceptable than RRSO for combined surgery given the potential for menopausal symptoms while recovering from effects of mastectomy.

    Benefits of OSGs42–44 include fluid informational exchange, continuous availability, greater access/anonymity and were also reported by our cohort. Our cohort reported increasing anxiety with OSGs and a preference for educational support groups (ESGs). ESGs involve face-to-face group activities where participants and clinicians share their experiences and expertise, along with a patient representative acting as the group spokesperson. Women found the opportunity to ask experts questions and meet other BRCA carriers face-to-face more helpful than OSGs. Although small randomised controlled trials (RCTs) have shown lower anxiety/depression with OSGs (compared with clinical care) in BC women,45 these results may not be generalisable to BRCA previvors unaffected by cancer. Large, well-designed RCTs comparing OSG with ESG are needed. Another gap we identified was support women needed to communicate to their children genetic test results and the complex decisions they faced. Options to address this may include customised information sheets/decision aids, offering family counselling. While family counselling is established for informing children of a parent’s cancer diagnosis,46 outcome data and pathways for this in a previvor setting are needed.

    Strengths of our study include a robust methodological approach using semistructured in-depth interviews until reaching data saturation, independent data analysis by two researchers and a comprehensive three-step coding process. Our sample was broad-based and included women who declined surgery, had a personal history of BC, parous/nulliparous, ascertainment from a variety of outpatient settings and different UK geographical locations. Limitations include that only two interviewees were non-Caucasian and there may be cultural nuances affecting the decision-making process in ethnic minorities. Also, women who had undergone RRM were interviewed retrospectively, ensuing a risk of recall bias.

    Medical, physical, psychological and social contextual factors influence the timing of risk-reducing surgeries. RRESDO offers premenopausal women who would otherwise delay/decline premenopausal oophorectomy a degree of OC risk reduction while avoiding the detrimental sequelae of early menopause. The addition of RRESDO as a two-stage surgical alternative to RRSO, adds an additional dimension to an already complex decision-making process, so it is possible it may increase length of time for women to come to a decision regarding OC prevention surgery. Women who prioritise maximising OC risk reduction favour selecting RRSO, whereas those who prioritised maintaining QoL and avoiding menopause preferred RRESDO. Our cohort of women expressed a clear interest in combined breast-and-ovarian prophylactic surgeries. Women managed in specialist FCC settings compared with non-specialist settings received better quality care, better HRT access and were more satisfied. There is need for centralising the care of women at risk of familial gynaecological cancers to centres within specialist-FCC services which are able to provide a more streamlined, holistic multidisciplinary approach.

    Acknowledgments

    We are grateful to all women took part in the interviews. We are grateful to the central trials coordinating team at the Centre for Experimental Cancer Medicine at QMUL, led by Kelly Mousa. We are grateful to the independent members of the trial steering committee (chaired by Mr Tim Mould) and the data monitoring committee (chaired by Professor Richard Edmondson) and central pathology committee (Professor Naveena Singh (chair), Professor W Glenn McCluggage, Dr Raji Ganesan, Dr Gareth Bryson, Dr Gareth Rowlands, Dr Rupali Arora). We acknowledge support provided by a number of charities and stakeholders including BRCA Umbrella (Caroline Presho), The Eve Appeal, Ovacome, Target Ovarian Cancer and Ovarian Cancer Action. GDE is supported through the NIHR Manchester Biomedical Research Centre (IS-BRC-1215–20007). We are grateful to all our collaborators of the PROTECTOR study: Dr Munaza Ahmed (North East Thames Cancer Genetics Service, Great Ormond Street Hospital NHS Foundation Trust), Dr Aarti Sharma (Cardiff and Vale UHB), Dr Gautam Mehra (Guy’s and St Thomas’ NHS Foundation Trust), Dr Adam Rosenthal (University College London Hospitals NHS Foundation Trust), Dr Ian Harley (Belfast Health & Social Care Trust), Dr Michelle Mackintosh & Prof Emma Crosbie (Manchester University NHS Foundation Trust), Professor Sadaf Ghaem-Maghami (Imperial College Healthcare NHS Trust), Professor Omer Devaja (Maidstone and Tunbridge Wells NHS Trust), Professor Sudha Sundar and Mr Janos Balega (Sandwell and West Birmingham Hospitals NHS Trust), Dr Tim Duncan (Norfolk and Norwich University Hospitals NHS Foundation Trust), Dr Iain Cameron (Gateshead Health NHS Foundation Trust), Dr Claire Newton (University Hospitals Bristol NHS Foundation Trust), Dr Sonali Kaushik (Brighton and Sussex University Hospitals NHS Trust), Dr Angela Brady (London North West Healthcare NHS Trust), Dr Supratik Chattopadhyay (University Hospitals of Leicester NHS Trust), Dr Natalia Povolotskaya (Portsmouth Hospitals NHS Trust), Dr Rema Iyer (East Kent Hospitals University NHS Trust), Dr Lucy Side (University Hospital Southampton NHS Foundation Trust), Dr Katie Snape (St George’s University Hospitals NHS Foundation Trust), Dr Anil Tailor (Royal Surrey County Hospital Foundation Trust), Dr Manon van Seters (Worcestershire Acute Hospital Trust), Dr Katherine Edey (Royal Devon & Exeter NHS Foundation Trust), Dr Sian Taylor (Liverpool Women’s Hospital NHS Foundation Trust), Dr Suma Kodiathodi (North Tees and Hartlepool NHS Foundation Trust), Dr Partha Sengupta (County Durham and Darlington NHS Foundation Trust), Dr Scott Fegan (NHS Lothian), Dr Karin Williamson (Nottingham University Hospitals NHS Trust), Dr Andrew Phillips (University Hospitals of Derby and Burton NHS Foundation Trust), Dr Mark Willett (East Lancashire Hospitals NHS Trust), Dr Tony Chalhoub (The Newcastle upon Tyne Hospitals NHS Foundation Trust), Dr Sanjay Rao (South Tees Hospitals NHS Foundation Trust), Dr Nicholas Matthews (South Tyneside and Sunderland NHS Foundation Trust), Dr Beena Abdul (Northampton General Hospitals NHS Trust), Dr Ibraheem Hamoodi (Northumbria Healthcare NHS Foundation Trust), Dr Claire Park (Royal United Hospitals Bath NHS Foundation Trust), Dr Jane Borley (Royal Cornwall Hospitals NHS Trust), Dr Richard Hutson (Leeds Teaching Hospitals NHS Trust), Dr Kerryn Lutchman-Singh (Swansea Bay University Health Board), Dr Richard Peevor (Betsi Cadwaladr University Health Board), Dr Mahalakshmi Gurumurthy (NHS Grampian), Dr Kalpana Ragupathy (NHS Tayside).

    References

    Supplementary materials

    • Supplementary Data

      This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Footnotes

    • Twitter @ProfManchanda

    • Collaborators The PROTECTOR team: Raji Ganesan; Gareth Bryson; Gareth Rowlands; Rupali Arora; Munaza Ahmed; Aarti Sharma; Gautam Mehra; Adam Rosenthal; Michelle Mackintosh; Sadaf Ghaem-Maghami; Omer Devaja; Sudha Sundar; Janos Balega; Tim Duncan; Claire Newton; Sonali Kaushik; Angela Brady; Supratik Chattopadhyay; Natalia Povolotskaya; Iain Cameron; Rema Iyer; Lucy Side; Katie Snape; Anil Tailor; Kavitha Thumuluru Madhuri; Katherine Edey; Sian Taylor; Manon van Seters; Suma Kodiathodi; Partha Sengupta; Scott Fegan; Karin Williamson; Andrew Phillips; Mark Willett; Tony Chalhoub; Sanjay Rao; Nicholas Matthews; Beena Abdul; Claire Park; Jane Borley; Ibraheem Hamoodi; Richard Hutson; Kerryn Lutchman-Singh; Richard Peevor; Mahalakshmi Gurumurthy; Kalpana Ragupathy; Emma Crosbie.

    • Contributors Conception of qualitative study: FG, RM. Qualitative design and development: FG, RM, DM. Qualitative data collection: FG. Trial management: FG, SR, CT, NS, GDE, UM, RL, ES, WGM, HH, RM. Data analysis: FG, SG, RM, DM. Preparation of tables and figures: FG, OE. Initial draft of manuscript: FG, RM, DM. Manuscript writing and approval: all authors.

    • Funding The study is supported by researchers at the Wolfson Institute of Preventive Medicine, Queen Mary University of London (C16420/A18066). This work was supported and funded by Barts and The London Charity and Rosetrees Trust.

    • Disclaimer The funding bodies had no role in the study design, data collection, analysis, interpretation or writing of the report or decision to submit for publication. The research team was independent of funders.

    • Competing interests RM declares research funding from Cancer Research UK and The Eve Appeal outside this work, an honorarium for grant review from Israel National Institute for Health Policy Research and honorarium for advisory board membership from Astrazeneca/MSD. RM is supported by an NHS Innovation Accelerator (NIA) Fellowship for population testing.

    • Patient consent for publication Not required.

    • Ethics approval The PROTECTOR Study received full ethics approval from London-Bloomsbury Research Ethics Committee (18/LO/0555). The study was registered with the International Standard Randomised Controlled Trial Number Register-ISRCTN 25173360 (https://doi.org/10.1186/ISRCTN25173360).

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data are available on reasonable request.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.