Management of breast cancer patients with BRCA gene mutations in Jordan: perspectives and challenges

ABSTRACT

Background

This paper explores and discusses local challenges oncologists face for diagnosing and managing breast cancer patients with BRCA gene mutations in Jordan.

Methods

A task force involving key opinion leaders, experts in the management of breast cancer, and stakeholders in healthcare systems where genetic testing is available in Jordan discussed current evidence and local real-life practice. The task force then formulated recommendations to achieve better patient outcomes and satisfaction based on evidence-based medicine and their clinical experience in BRCA-mutated breast cancer management.

Results and conclusion

Eligibility of patients for genetic testing, physician acceptance and willingness to integrate genetic testing into routine practice is encouraging but remains restricted by testing availability and financial coverage. Until more data is available, genetic testing should be targeted for breast cancer patients based on tumor subtypes, as well as family and personal history of cancer, as per international guidelines. Whenever possible, genetic testing should aim to detect all actionable genes through a multigene panel including BRCA1/2. Major challenges faced in clinical practice in Jordan include fear of genetic discrimination and social stigmatization, as well as hesitancy toward risk-reducing surgery. Pre-testing counseling is therefore critical to promote acceptance of genetic testing. Since geneticists are in short supply in Jordan, genetic counseling can be offered through a specially trained genetic counselor or through a hybrid system that includes oncologist-based counselling. In addition to cancer prevention, germline genetic testing may assist in the selection of specific anti-cancer therapy, such as PARP inhibitors, in patients with BRCA1/2 mutation. Nationwide initiatives are also needed to ensure access to PARP inhibition therapy and provide financial coverage for genetic screening, mastectomies and reconstructive surgery across Jordan.

KEYWORDS:

• Breast cancer
• HER2-negative
• germline BRCA mutation
• BRCA1
• BRCA2
• genetic testing

1. Introduction

Female breast cancer is the most commonly diagnosed cancer globally, accounting for an estimated 2.3 million new cases and 6.9% of all cancer deaths in 2020 [1]. This is reflected in Jordan, where breast cancer single-handedly accounted for around 40% of all cancers among women in 2018 [2]. Most notably, women with breast cancer in Jordan have more advanced disease and younger age at presentation than their counterparts in Western/industrialized countries [3].

The majority of breast cancer tumors, be their occurring in BRCA1/2 carriers or not, are human epidermal growth factor receptor 2 (HER2)-negative [4,5]. The prevalence of germline breast cancer gene (BRCA)-mutations (gBRCAm) varies widely among breast cancer patients (of both sexes) across the world, ranging from 1.8% to 36.9% [6]. This variability is due to small number of patients included in the studies, poor reporting of gBRCA mutational status and often ambiguous basis of selection [6]. Moreover, major inconsistencies exist in the methodology, reporting and volume of clinical testing for BRCA mutations between laboratories around the world, further compounding the variability of gBRCAm prevalence [7]. Data from breast cancer patients treated at King Hussein Cancer Center (KHCC) – Jordan supports previous estimates, with around 17.5% of samples reportedly HER2/neu positive [3,8]. Regardless, BRCA mutations have been clearly associated with clinical outcomes and prognosis in HER2- breast cancer [9,10]. Moreover, evidence strongly supports the need for BRCA mutation screening in all high-risk breast cancer patients, regardless of family history [11–17].

The National Comprehensive Cancer Network (NCCN) 2023 guidelines currently recommend that genetic testing for risk assessment should be considered only when genetic testing will carry clinical implications; genetic testing is therefore counseled for patients with personal history of breast cancer who are 50 years or younger, or those of any age who fulfill testing criteria, namely, 1) a high-risk pathology/histology (triple-negative breast cancer (TNBC), among others); 2) a treatment indication (to aid in systemic therapy such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors and surgical decision-making; 3) male breast cancer; 4) specific ancestry (Ashkenazi Jewish), or 5) family history of breast cancer and/or other relevant malignancies (pancreatic, ovarian, metastatic/high-risk prostate cancer) [18,19]. With regard to treatment, PARP inhibitors are recommended for all patients with HER2- breast cancer carrying a gBRCA with recurrent or stage IV disease and could also be considered for select patients in the adjuvant setting [18,19].

By contrast, clinical practice in Jordan in particular, and the Arab world in general, is governed by the cost and sporadic availability of therapeutic and/or diagnostic resources [20]; Chemotherapy remains the prevailing treatment choice in the first- and second-line settings for patients with HER2- breast cancer with gBRCA mutation. PARP inhibitors are costly and not widely available and are therefore only considered after failure of chemotherapy. Breast cancer patients in Jordan with gBRCA1/2 mutations will generally meet with an oncologist to address risk reducing surgery and further disease-related therapy (like using PARP inhibitors), while carriers (relatives) meet with genetic counselor and are given the option of risk-reducing surgeries or surveillance. Most patients follow the recommendations of their physicians, who are experienced and up to date with the growing data in the field. Surveillance, even for BRCA1/2 variants, is an acceptable practice if the patient opted to do so. Recommendations on lower risk genes are lacking and need to be individualized, taking into consideration patients’ personal and family history of breast or any other cancers. However, genetic testing is limited to a single public institution in Jordan due to cost considerations as well as lack of local expertise. Currently, more than 95% of breast cancer patients treated at KHCC and eligible for testing do so as per international guidelines. The cost of multi-gene panel genetic testing in the public sector in Jordan is fully covered for patients and is available for a minimal fee for their relatives. Genetic testing is also available in the private sector, albeit at a high cost to the patient. That being said, both genetic counseling as well as patient awareness and acceptance of genetic screening lag behind international standards of care.

In this view, this paper offers a consensus on the proper management of the disease addressing most unmet needs such as drug availability, testing availability, impact on the patient, and acceptance of risk-reducing surgeries. Ultimately, this paper aims to help oncologists, genetic counselors, and pathologists to achieve better patient outcomes and satisfaction through sharing experts’ recommendations and best practices. This project can be a step forward toward a recognized guidance for all trained healthcare professionals for better management of breast cancer patients with BRCA gene mutations in Jordan.

2. Methodology

A task force of healthcare professionals was assembled by inviting key opinion leaders, experts in the management of breast cancer, and stakeholders in healthcare systems where genetic testing is available in Jordan. All authors were members of the task force, which included Internal Medicine and Medical Oncologists, the Deputy Director General of the only center offering genetic testing in Jordan and other key stakeholders implicated in oncology. The task force met in 2022 to initiate the discussions and for the presentation of evidence and insights. The authors also reviewed published literature using keywords such as “‘BRCA1 or BRCA2 gene mutations’, ‘breast cancer’, ‘genetic counseling’, ‘PARP inhibitor’ and ‘Jordan’. The reference lists of selected articles were used to identify further references, which were also generated from the author’s knowledge of the field. The task force finally undertook the analysis of the Jordanian and regional situations, extracting local perspectives and challenges based on published literature, clinical practice, international guidelines, best practices, clinical gaps as well as available treatments and workup methodologies.

3. Results

3.1. Epidemiology data in Jordan and other Arab countries

While scant, some data have been published on gBRCAm in breast cancer patients in the Arab world. A systematic review and meta-analysis of BRCA mutations among hereditary breast cancer patients reported a pooled prevalence of 21% in Arab countries; 11% BRCA1 alone and 17% BRCA2 alone [21]. To note that elimination of studies with high risk of bias yielded a lower prevalence of BRCA mutations (11%), comparable to that reported in the literature [21]. However, existing evidence is heterogenous and sometimes conflicting, even in the same population, reflecting the lack of a standardized and universal approach for patient selection and genetic testing/screening in Arab countries [20]. The heterogeneity of available data calls for the conduction of large-scale well-designed studies in the region.

Regardless, a glance at studies published from Jordan and neighboring countries reveals the high prevalence of gBRCAm in local populations. A study from Saudi Arabia reported BRCA1 mutations in 11% and BRCA2 mutations in 2% of breast cancer patients, while 11% had variants of uncertain significance (VUS) [13]. TNBC and family history were associated with higher mutation rates [13]. Another Saudi study reported an overall prevalence of 10.2% of gBRCAm in women with breast cancer [22]. In Jordan, several studies describe the prevalence of gBRCAm in breast cancer patients; 12.2% of cases had pathogenic or likely pathogenic gBRCAm in one study of 616 young patients undergoing genetic testing and counseling. Higher mutation rates were linked to several factors, among which was triple-negative disease, and a family history of breast cancer (2 or more family members) [15]. Another study focusing on high-risk breast cancer patients reported a prevalence of recurrent pathogenic mutations of 14.5%, while 3.5% were newly detected mutations [16]. Recent results of genetic testing in 1197 patients with breast cancer in Jordan reflected the increase in the rate of VUS in local populations (9.2%), 71.8% of which were BRCA2 [17].

3.2. Screening and risk reduction

3.2.1. Who should be screened, and how?

gBRCA mutations carry prognostic value in HER2- breast cancer [9]. Data from the German PRAEGNANT registry showed a gBRCA mutation rate of around 5%, with improved prognosis in terms of overall survival (OS) in patients with HER2- metastatic gBRCAm breast cancer previously treated with chemotherapy [9]. Global results from the real-world, observational BREAKOUT study reported that a higher prevalence of germline BRCA mutations of 10.4% in patients with HER2-negative metastatic breast cancer and no risk factors for gBRCA mutation [23]. The high prevalence of BRCA mutations was evident in Arab countries as well. A 12.9% of high-risk breast cancer patients from Saudi Arabia had BRCA mutations [13]. In Jordan, the prevalence of pathogenic or likely pathogenic gBRCAm in breast cancer patients was also reportedly high [15]; Recurrent pathogenic mutations can be observed in 14.5% of cases [16], and the rate of VUS is on the rise [17].

Though most clinician use guidelines-based testing to include patients with high probability of harboring a cancer-predisposing gene, some advocate universal testing of all women with breast cancer. In fact, recommendations of universal testing for all breast cancer patients have been provided by some societies (such as The American Society of Breast Surgeons [24], with reported acceptance and clinical value of this approach in daily practice [25]. Evidence to support the need for universal genetic testing of all breast cancer patients at diagnosis regardless of family history has been published [11,13–17,26]. Studies show that BRCA1/2 mutations in TNBC are not restricted to young women or patients with a positive family history of cancer [11,27]. Moreover, universal genetic testing following the diagnosis of breast cancer for the detection of clinically significant germline pathogenic variants is feasible and accepted by both patients and physicians [26]. More importantly, 18 (58%) of the 31 identified pathogenic germline variants did not meet current genetic testing eligibility guidelines [26]. It is becoming increasingly evident that by applying restrictive testing guidelines, an unacceptable number of patients (up to 50%) with actionable variants are missed [28–30], supporting universal genetic testing in this patient population.

That being said, the latest NCCN 2023 guidelines only recommend genetic testing for risk assessment when it is likely to affect the management and/or treatment of the patient in question or close family members; genetic testing is therefore counseled for patients with personal history of breast cancer who are 50 years or younger, or those of any age who fulfill testing criteria, namely, 1) a high-risk pathology/histology (triple-negative breast cancer (TNBC), among others); 2) a treatment indication (to aid in systemic therapy such as poly adenosine diphosphate-ribose polymerase (PARP) inhibitors and surgical decision-making; 3) male breast cancer; 4) specific ancestry (Ashkenazi Jewish), or 5) family history of breast cancer and/or other relevant malignancies (pancreatic, ovarian, metastatic/high-risk prostate cancer). It is also recommended that all patients with recurrent or metastatic breast cancer be assessed for germline BRCA1/2 mutations to identify candidates for adjuvant PARP inhibitor therapy [18,19].

Candidates for PARP inhibitor therapy should be determined based on detection of BRCA mutation through germline sequencing. Multigene testing through next-generation sequencing (NGS) technology or Multiplex ligation-dependent probe amplification (MLPA) can also be considered, particularly for hereditary cancer testing of at-risk patients and their families. In this regard, the NCCN guidelines emphasize the importance of phenotype-directed tailored testing based on personal and family history to preserve the efficiency and cost-effectiveness of multigene panel test. Through this, the possibility of detecting a pathogenic or likely pathogenic variant and ensuring clinical actionability is maximized. By exploring recurring genetic mutations, clinicians from the region show continued attempts to establish mutational panels for each country’s population as a first step to tackling the financial burden of genetic testing [31,32]. Population-specific mutational panels are necessary as common mutations in one country are rarely, if ever, applicable to another [16].

Comprehensive genomic profiling of breast cancer tumors can lead to the identification of clinically actionable alterations in patients with advanced breast cancers [33]. Cost-effectiveness evaluations of genetic testing have shown that genetic screening for BRCA in unselected breast cancer patients was cost-effective in high and upper-middle income countries, but not in low-middle income countries [34,35]. Such cost-effectiveness studies are generally lacking in the Arab region. However, in the absence of the adequate infrastructure and human resources necessary for universal genetic testing, the panel believes genetic testing should currently be considered for high-risk individuals only, as described in the NCCN 2023 guidelines (i.e. patient is 50 years or younger, is at risk for hereditary breast cancer owing to personal history, family history, or ancestry (at any age), has high-risk pathology/histology such as TNBC (at any age), has male breast cancer (at any age), or is a candidate for adjuvant PARP inhibitor or risk-reducing surgery (at any age), where genetic testing is likely to affect the management and/or treatment of the patient in question or close family members). Moreover, genetic testing in breast cancer should not be restricted to BRCA1/2 but rather should be done through a multigene panel, including BRCA1/2. This is necessary seeing as almost 50% of actionable genes would be missed if genetic screening is restricted to current guidelines’ testing criteria [28,29].

Treatment costs for breast cancer increase with more advanced stages in Jordan [36]. As a result, the expert panel believes that genetic testing, reconstructive surgery, and genetic screening of patient families would prove cost-effective compared to the treatment of metastatic cancer. One study estimates cost savings of 75% when counseling and genetic testing was undertaken for all breast cancer patients prior to making any diagnostic-therapeutic decisions [37]. On this basis, guiding and urging the Jordanian ministry of health to cover the cost of genetic screening, counseling, mastectomies and reconstructive surgery becomes a keen valuable national interest.

3.2.2. Recommendations for risk reduction in carriers of gBRCAm

As previously mentioned, surveillance is an acceptable practice even for BRCA1/2 variants if the patient opted to do so. While the optimal surveillance approach (imaging modalities and surveillance intervals) is yet to be established, individuals at high risk for beast cancer are eligible for yearly screening. As per NCCN 2023 guidelines for genetic/familial high-risk assessment [19], MRI (with contrast) is generally preferred for younger individuals (<29 years) as it minimizes the radiation risks of mammography and has higher sensitivity for tumor detection, despite its potential higher false-positive results. Individuals aged 30 or more should undergo both an annual mammogram and MRI with contrast. That being said, risk-reducing strategies such as prophylactic surgery and chemoprevention are also available, as discussed in the following subsections.

3.3. Prophylactic surgery

In addition to counseling patients to lead a healthy lifestyle and undergo regular breast exams (physical and mammograms) to reduce the risk of breast cancer, risk-reducing interventions, including bilateral mastectomies and salpingo-oophorectomies are both effective in BRCA-mutated disease and should be considered [38–41]. Risk-reducing surgery may be offered to all individuals carrying pathogenic or likely pathogenic BRCA variants, including not only breast cancer patients but also their relatives. Overall, the NCCN details several indications for risk-reducing mastectomy, which should generally be reserved for individuals with a pathogenic/likely pathogenic mutation (not for VUS) conferring a high risk for breast cancer or compelling family history. It should be noted that risk reduction is dependent solely on conducting a complete mastectomy, regardless of whether the nipple is spared. Breast-conserving surgery could also be offered to breast cancer patients with gBRCAm seeing as it is associated with comparable clinical outcomes to mastectomy (i.e. incidence of contralateral breast cancer, disease-free survival, metastasis-free survival, breast cancer-specific survival and OS), albeit with a potentially higher risk of local recurrence [42–44].

In Jordan, one study reported that the detection of genetic VUS had no notable implication on clinical practice, be it on therapeutic or prophylactic surgical decisions [17]. Breast-conserving surgery was conducted in close to half of patients with non-metastatic disease. Most notably, prophylactic surgery is done in very few patients [17]. This perfectly illustrates the psycho-social challenges faced in Jordan, where fear of social stigma and female hesitancy toward prophylactic surgery significantly hinder clinical practice. Patient hesitancy and potential solutions are discussed in more detail in Section 3.6.2.

3.4. Beyond the cut: chemoprevention

Risk-reducing agents (chemoprevention) can also be used (tamoxifen for premenopausal women, tamoxifen or raloxifene or aromatase inhibitors for postmenopausal) [45]. RCTs support that clinically relevant risk reduction can be achieved with the use of tamoxifen or equivalent raloxifene, as well as aromatase inhibitors [46,47]. Regardless of the clinical benefit of these agents, their risk reduction potential is poorly studied in patients carrying BRCA mutations. Moreover, long-term use of these drugs is not currently advised due to potentially emerging safety concerns as robust data beyond 5 years are not yet available.

3.5. Emerging role of PARP inhibitors in gBRCAm HER2-negative advanced breast cancer

Several PARP inhibitors were investigated by randomized controlled clinical trials in patients with gBRCAm. The OlympiAD trial demonstrated that olaparib ensured better progression-free survival (PFS), but not OS, compared to single agent palliative chemotherapy (capecitabine, eribulin or vinorelbine) in patients with gBRCA1/2m [48,49]. The EMBRACA trial investigated another PARP inhibitor, Talazoparib, in patients with HER2-negative locally advanced or metastatic breast cancer and deleterious or suspected deleterious germline BRCA1/2 mutation. This trial also demonstrated a significant improvement in PFS, but not OS, with the use of the PARP inhibitor compared to single-agent chemotherapy (capecitabine, eribulin, gemcitabine or vinorelbine) [50,51]. The efficacy, safety and tolerability of talazoparib and olaparib were found to be comparable by a network meta-analysis of data from both clinical trials [52]. The BROCADE3 trial was conducted in a similar patient population of pathogenic gBRCA1/2m and advanced HER2-negative breast cancer. The study reported that the addition of the PARP inhibitor veliparib to platinum-based doublet chemotherapy, with continuation as monotherapy if chemotherapy was stopped, leads to significant and durable PFS improvement [53,54]. Further details on these trials can be found summarized in the review by Edaily and Abdel-Razeq [55].

PARP inhibitors are currently recommended by the NCCN guidelines for all patients carrying a gBRCA mutation with recurrent or stage IV disease and select patients in the adjuvant setting [18,19]. Overall, available evidence supports the role of PARP inhibitors in HER2-negative gBRCAm locally advanced or metastatic breast cancer, where they ensure an improvement in PFS compared to other therapy, even in patients who had previous chemotherapy [56]. In addition to this, PARP inhibition most likely positively influences OS and tumor response rates in this patient population while incurring toxicity comparable to that of chemotherapy [56]. PARP inhibitors also exhibited a survival advantage in early stage high-risk HER2- breast cancer with gBRCA1/2 pathogenic or likely pathogenic variants when used in the adjuvant setting; patients in the OlympiA trial receiving adjuvant olaparib had significantly longer survival free of invasive or distant disease and longer overall survival compared to placebo [57,58]. Despite this, chemotherapy remains the treatment of choice in the first- and second-line settings for patients in Jordan. PARP inhibitors are only considered after failure of chemotherapy due to their financial burden and limited availability across the country. Immune checkpoint inhibitors are also considered for patients who are programmed death ligand 1 (PD-L1) positive. The experts recognize the role of PARP inhibitors in advanced HER2-negative breast cancer with gBRCAm as first-line therapy in the ideal scenario where the drug is available, affordable and cost-effective.

3.6. Local challenges facing the management of breast cancer patients with BRCA gene mutations

3.6.1. Availability of genetic testing in Jordan

Multi-gene panel genetic testing, including BRCA1/2, is only offered at KHCC and is generally not available in other governmental institutions due to cost considerations and lack of local expertise. However, it is available in the private sector. Genetic testing is done through a third party outside of Jordan. To note that the cost of genetic testing at KHCC is fully covered for patients, while family members of patients can also be tested for minimal fees. Although multigene panel genetic testing is preferred for all breast cancer patients regardless of age, family and personal history or disease subtype, the panel recognizes that it might be best to initially introduce genetic testing in Jordan for high-risk patients as per NCCN guidelines criteria, as opposed to universal testing. Once genetic screening infrastructure (testing facilities, genetic counselors, financial coverage for patients and relatives) is established, efforts can be expanded to implement universal testing for all breast cancer patients.

This approach will be mostly likely necessary as a precautionary measure against challenges that are foreseen in case universal genetic testing is immediately implemented, namely:

• An increase in VUS rate and the subsequent need for knowledgeable physicians capable of interpreting the results of genetic testing, as well as the need to have a mechanism in place for follow-up on a case-by-case basis.

• High financial burden.

• Limited availability of genetic testing in institutions other than KHCC.

• Limited drug availability across Jordan and by extension, limited actionability of variants detected through genetic testing.

3.6.2. Psycho-social barriers to genetic testing

While the clinical and economic advantages of genetic testing are irrefutable (particularly among high-risk breast cancer candidates), anecdotal patient interactions and the task force member’s own experience as medical oncologists show that patients and their families in Arab countries such as Jordan do not readily embrace it. In addition to the financial burden incurred for uninsured patients in Jordan, psycho-social factors, primarily fear of stigmatization and familial labeling as being at high risk of malignancies, play a considerable role in genetic testing acceptance and result dissemination [20]. Studies show that while patients are generally satisfied with their decision to undergo a contralateral risk-reducing mastectomy, they often suffer psycho-social consequences such as diminished satisfaction with body image and sexual feelings [38]. It is therefore important to consider breast-conserving strategies, particularly among younger patients. A recent meta-analysis found a higher risk of local recurrence with breast-conserving surgery in BRCA-mutated cancers, albeit with no significant impact on patient survival [42].

Consistently, local clinical experience is fraught with patient refusal of genetic testing by patients on the basis of several considerations (listed below, based on anecdotal real-life evidence), all of which reflect the lack of awareness of genetic testing and prophylactic surgery among the population.

• Lack of interest to identify familial genetic problems.

• Lack of consent to undergo prophylactic surgery in case of positive results.

• Incapacity to cover the cost of genetic testing and/or treatment.

• Fear of social stigma related to mutation carriage.

Efforts should focus on promoting awareness of the benefit of genetic testing as well as the safety, efficacy and breast-preserving capacity of prophylactic mastectomy with reconstructive surgery, both among breast cancer patients and the public. Through this, national momentum and initiatives could be generated to drive relevant stakeholders (such as the ministry of health) to provide financial coverage for genetic testing and reconstructive surgery (breast implants), in addition to the cost and surgical skills needed for mastectomies.

3.6.3. Availability of genetic counseling in Jordan

The physician’s approach to genetic testing and patient communication plays an important role in promoting patient acceptance and knowledge of genetic screening while also reducing fear and anxiety [59]. There is a clear gap between need and availability of genetic counseling, even in developed/industrialized countries [60]. It is therefore crucial to train medical oncologists and other healthcare professionals (e.g. nurses, breast surgeons, pharmacists) to provide genetic counseling and improve patient awareness and referral rates [61,62].

Geneticists are in short supply in Jordan, which leads to oncologists having to personally deliver genetic counseling. A hybrid system (such as that followed in KHCC) might be most applicable in Jordan; This system relies on both genetic counselor-based and oncologist-based counseling. Local efforts can be expanded to include other specialties that can be trained to provide genetic counseling such as pharmacists, nurses and technologists. Genetic counseling improves patient engagement, reduces breast cancer worry, anxiety, and depression and improves understanding of risk, although it decreases intention for testing [63,64]. The experts thus recognize the importance of establishing assigned genetic counseling unit where comprehensive educational and psycho-social support as well as sufficient time can be spared for each patient, regardless of which specialist delivers the counseling.

3.6.4. All hands on deck: supporting local initiatives

Several stakeholders could and should be implicated in the support of preventive/prophylactic approaches in HER2-negative breast cancer with gBRCAm. The Jordanian Breast Cancer Program (JBCP) could support genetic testing initiatives by possibly providing some coverage as well as fundraising to cover for patient in need of reconstructive surgeries. Lastly, healthcare institutions could promote and support initiatives calling for universal, or at least expanded, genetic testing.

4. Conclusion

A significant number of patients being eligible for BRCA testing in Jordan. Physician acceptance of and willingness to integrate genetic testing into routine practice is encouraging but remains restricted by testing availability and financial coverage. The panel recognizes that genetic testing should be initially introduced in Jordan for high-risk patients as per NCCN 2023 guidelines criteria, as opposed to universal testing. Note that genetic testing in breast cancer should not be restricted to BRCA1/2 but rather should be done through a multigene panel including BRCA1/2 to ensure detection of all actionable genes. However, fear of genetic discrimination, or family labeling of BRCA mutation carriage is a major challenge in Jordan and a prominent reason for genetic testing refusal. Moreover, some patients refuse risk-reducing surgery, which also affects genetic testing rates. It is therefore important to counsel patients prior to genetic testing to determine their acceptance of its implications on clinical management. Since geneticists are in short supply in Jordan, genetic counseling can be offered through a specially trained genetic counselor or through a hybrid system. Moreover, efforts can be expanded to include other specialties that can be trained to provide genetic counseling such as pharmacists, nurses and technologists. Considering their expected cost-effectiveness, nationwide initiatives to provide financial coverage for genetic screening (of patients and their families), mastectomies and reconstructive surgery should be pursued.

Declaration of financial/other relationships

H Abdel-Razeq has received an institutional research grant from Pfizer. S Abbasi has given lectures for Pfizer, Roche and MSD. H Abduelah has given lectures for Novartis, Pfizer, Roche and Hikma; and has participated in clinical studies sponsored by Hikma. S Al-Masri and J Debs are paid employees at Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

The primary author was responsible for the concept of the paper and led the project. All authors have written parts of and have reviewed the whole manuscript.

Acknowledgments

Medical writing and editorial support of the manuscript was provided by Nancy Al Akkary (MSc, BSc) and Racha Aaraj, Pharm D, MSc, MPH from Phoenix Clinical Research and was funded by Pfizer.

Additional information

Funding

This paper was funded by Pfizer. The authors retained the editorial process, including the discussion at all times. There was no financial reward associated with writing the paper. Phoenix Clinical Research provided editorial and medical writing assistance for the preparation of this manuscript based on the Good Publication Practice (GPP3) and the ICMJE requirements and was funder by Pfizer. The views and opinions expressed are those of the authors. Pfizer has had no influence over the content other than a review of the paper for medical accuracy.