Recommendations of Health Care Professionals on the Issue of Breastfeeding in BRCA Carriers

Table of Contents

1.0 Introduction

2.0 Recommendations

3.0 Key Information to Support Recommendations

  3.1 Background

  3.2 Population Feeding Practices and Beliefs

1.0 Introduction

BReast CAncer gene (BRCA)1 and BRCA2 gene germline pathogenic variants are associated with a substantially increased risk of developing breast and ovarian cancers, which are among the most prevalent and life-threatening malignancies affecting women worldwide. The global occurrence of BRCA1 and BRCA2 pathogenic variants is estimated to range from 1 in 300 to 1 in 450 women. ¹ Founder mutations of BRCA1/2 have been identified across diverse ethnic cohorts, spanning regions such as the Netherlands, Sweden, Hungary, Iceland, Italy, France, South Africa, Pakistan, and Asia. ² Moreover, these variants have been documented among specific demographic groups, including French Canadians, Latinx, and African Americans, reaching up to 2.5% among Ashkenazi Jewish population.^1,3,4 Women who carry BRCA1/2 pathogenic variants confront a markedly heightened lifetime risk of breast cancer, surpassing 60%, as well as an increased risk of ovarian cancer, ranging from approximately 40–60% for BRCA1 mutations and 15–30% for BRCA2 mutations. ²

Several modalities have been reported to decrease cancer risk in BRCA carriers, including oral contraception, bilateral tubal ligation, and breastfeeding. ⁵ Breastfeeding, a fundamental aspect of postpartum care, is renowned for its multifaceted health benefits for both neonates and mothers. It has been extensively documented to confer significant neonatal advantages, including neurobehavioral benefits, stimulation of optimal development and function of the gastrointestinal system, protection from infectious diseases, decreased mortality, and to enhanced maternal postpartum recovery. ⁶ Maternal benefits of breastfeeding include reduced risk of postpartum blood loss, long-term cardioprotective effects, and decreased risk for type 2 diabetes. ⁷ Among these advantages, one of the most compelling is a decrease in the risk of breast and ovarian cancer, including in women carrying BRCA1/2 mutations. ⁵ However, a notable gap exists in the understanding of the recommended postpartum surveillance and guidance for pregnant and breastfeeding BRCA carriers, often involving clinical examinations or ultrasound follow-up^8,9.

Thus, the aim of this study was to delve into the recommendations provided by health care professionals regarding breastfeeding in BRCA carriers.

2.0 Recommendations

This online survey adhered to the guidelines outlined in the Checklist for Reporting Results of internet E-Surveys (CHERRIES). ¹⁰ Since no validated instruments existed for the specific subject under investigation, the survey instrument was custom-developed in collaboration with the Ministry of Health and managers from the “Good BRCA genes-a support and information association for BRCA carriers” association. This collaboration drew upon their expertise and current literature relevant to the study.

The survey commenced with an introductory section elucidating the overarching objective: to assess the health care experiences of women aged 18 years and older carrying the BRCA1/2 pathogenic variants. Prior to gaining access to the survey questionnaire, participants underwent an informed consent process. This process involved a comprehensive explanation of the survey's contents, identification of the principal investigators, and clarification of the anonymous nature of the survey. Participants were informed about the anticipated completion time and the nonmandatory nature of the questions. Additionally, participants were duly apprised that the findings would be summarized and published in a scholarly article (Supplementary Document 1).

The questionnaire itself comprised three main sections. The first section gathered demographic information, including age, marital status, religious affiliation, residence, health maintenance organization (HMO) membership, age at BRCA carrier diagnosis, and personal and family cancer history. The second section focused on the process leading to genetic BRCA testing, examining factors such as the positive diagnosis origin, pretesting explanation quality, and aspects related to the delivery of test results. The third section evaluated the quality of recommended medical follow-up and explanations regarding various issues. The survey was administered in Hebrew, with a translated version available in Supplementary Document 1.

The survey employed a fixed set of questions without adaptive questioning processes. Nonresponse options, tracking cookies, and IP addresses were excluded, and metrics such as unique site visitor counts were not computed. Because of its voluntary and anonymous nature, the survey was deemed exempt from institutional review board approval after consultation with the Helsinki Committee at Carmel Medical Center.

The survey link was initially shared through the “Good BRCA Genes” association's Facebook page, reaching approximately 2000 followers. Subsequent dissemination occurred organically through reader sharing without paid advertising. Responses were collected through Google Forms from January to March 2023.

For the current analysis, women aged over 45 years at the time of positive BRCA diagnosis, as well as respondents indicating that the topic of pregnancy and breastfeeding was irrelevant for them, were excluded. A comparison was performed between women satisfied with explanations provided by health professionals regarding pregnancy and breastfeeding (satisfaction levels of 4–5 on a Likert scale), to the remaining cohort. Open-ended responses were independently categorized by two investigators (L.S. and M.E.) using an inductive approach.

Data presentation involved categorical data expressed as numbers (percentages) and continuous variables as means ± standard deviations. Statistical analyses employed student’s t-test or Fisher’s exact test, as appropriate. A p<0.05 was considered statistically significant.

3.0 Key Information to Support Recommendations

Out of the 689 BRCA carriers who took part in the survey, 301 individuals were excluded from the analysis. This exclusion comprised 111 respondents who were over 45 years old at the time of their genetic diagnosis, an additional 103 who indicated that the topic of pregnancy and breastfeeding was not applicable to them, and an additional 87 who did not provide a response to the question regarding their satisfaction with the relevant explanation.

The study population comprised the remaining 388 relevant participants. The average current age of the participants was 37.6 ± 7.3 years, and the mean age at which BRCA diagnosis occurred was 30.5 ± 6.2 years. Among the participants, 346 (89.2%) identified as of Ashkenazi Jewish origin, 208 (53.6%) were affiliated with Clalit HMO (the largest Israeli HMO), and 201 (51.8%) were residents of the central region of Israel. Personal cancer history was reported by 86 individuals (22.2%), 352 participants (90.7%) had a familial history of cancer, and 258 (66.5%) were under the care of a designated carrier clinic.

Among the 388 participants, 233 (60.0%) expressed dissatisfaction with explanations provided by health professionals regarding pregnancy and breastfeeding. A comparison of demographic and medical characteristics between women satisfied and those dissatisfied with the explanations is presented in Table 1. Women reporting dissatisfaction with explanations regarding pregnancy and breastfeeding were younger (36.8 ± 7.0 years) compared to those satisfied with the explanations (38.8 ± 7.6 years, p = 0.0081). No differences were observed in terms of the age of BRCA diagnosis, Ashkenazi Jewish origin, residence in the center of the country, affiliation with Clalit HMO, personal or familial cancer history, or rates of follow-up in a designated carrier clinic.

Discussion

The results of this analysis spotlight a significant gap in the knowledge and practice of health care professionals with regard to breastfeeding recommendations for BRCA carriers. This is a cause for concern, since the evidence shows that breastfeeding can play a pivotal role in reducing the cancer risk in these women. ⁵ The consequences of such disparities can be profound, affecting the long-term health and well-being of BRCA carriers.

A plausible explanation for this knowledge gap may be linked to the inconsistencies in the medical management of pregnant and breastfeeding BRCA carriers. A recent review of surveillance guidelines and recommendations revealed several controversies and open questions in the management of cancer-free carriers. ⁹ In a review of 13 national and international guidelines, most did not include any recommendations regarding pregnancy and breastfeeding. The Dutch NABON (Nationaal Borstkanker Overleg Nederland) guidelines suggest self-examination and clinical examination every 6 months, whereas the Austrian clinical practice guideline (updated 2017) recommends sonography in three-month intervals and MRI not earlier than two months after lactation has ceased. ⁹

Notwithstanding the numerous advantages of breastfeeding for both maternal and neonatal health, there is no dispute regarding the protective impact of breastfeeding on the risk of ovarian and breast cancer in BRCA carriers. A systematic review conducted in 2013 investigated the influence of various factors on cancer risk in individuals carrying BRCA1 and BRCA2 mutations. ⁵ The review encompassed four case—control studies and two cohort studies focusing on the breast cancer-protective effects of breastfeeding. Among these, one study revealed a reduced risk for those who had ever breastfed compared with those who had never breastfed (OR = 0.76; 95% CI = 0.61 to 0.95), and all four case—control articles demonstrated a 32–50% decrease in risk for those breastfeeding for more than 1 year compared to those who had never breastfed. Regarding the impact of breastfeeding on the risk of ovarian cancer, among the two overlapping case—control samples and one cohort study, only one reported a statistically significant reduction in ovarian cancer risk for those who had ever breastfed compared to those who had never breastfed (OR = 0.74; 95% CI = 0.56 to 0.97), and for those breastfeeding for more than 1 year compared with those who had never breastfed (OR = 0.64; 95% CI = 0.47 to 0.91). ¹¹

Therefore, the available evidence strongly supports the positive impact of breastfeeding for at least 1 year on reducing cancer risks in BRCA carriers. This stands in stark contrast to the findings in our study, where more than three-quarters of the carriers received no information on the subject, and 8% of respondents to an open question reported being advised to avoid, discontinue, or limit breastfeeding.

The unexpected recommendations to avoid or limit breastfeeding could be related to the concern that augmented breast tissue and vascular flow changes associated with breastfeeding might impair the interpretation of imaging techniques.^12,13 The available screening methods come with specific limitations. For instance, mammography may yield increased false positives because of the alterations in breast density and vascular flow.^12,13 The use of breast MRI during breastfeeding is associated with gadolinium absorption by the child's gut, though this absorption is expected to be minimal. Notably, breast ultrasound exhibits the lowest specificity among breast imaging modalities, standing at 90.5%. ¹⁴ Nevertheless, the sensitivity of breast imaging for the detection of malignancy during pregnancy and lactation is high, up to 100%. ¹³

Limited evidence provides guidance to clinicians regarding the appropriate screening procedures specific for BRCA carriers during pregnancy or breastfeeding. A comprehensive review from 2017, delving into the safety and efficacy of breast cancer screening modalities for women with BRCA mutations who are pregnant or breastfeeding, has drawn recommendations from the latest published literature and expert opinions. ² This review indicates a lack of clear evidence supporting the efficacy of mammography or breast MRI as viable screening tools during this specific period. Consequently, it is considered reasonable to postpone initiating breast imaging with either mammography or breast MRI until 6–8 weeks after weaning, especially if the woman plans to breastfeed for less than 6 months postpartum. For women with BRCA mutations who continue breastfeeding, the authors recommend practicing breast awareness and undergoing clinical breast examinations every 6 months. In addition, for women planning to breastfeed for more than 6 months postpartum, breast MRI or mammography can be resumed (the latter for women above the age of 30). To mitigate mammographic density, it is advised to breastfeed or pump immediately before obtaining the mammogram. Importantly, no guidelines advocate for women to avoid or discontinue breastfeeding.

As BRCA mutations affect a significant portion of the population, the imperative to raise awareness among health care personnel regarding the benefits of breastfeeding for these women cannot be overstated. Failure to provide adequate guidance on breastfeeding to this high-risk group not only represents a missed opportunity to potentially reduce cancer risk but also raises ethical questions about the quality and equity of health care provided to these individuals.

To bridge this knowledge gap and improve care for BRCA carriers, multiple steps are warranted:

Educational Initiatives: Health care institutions and professional organizations should develop educational programs and guidelines specifically tailored to health care professionals, focusing on breastfeeding recommendations for BRCA carriers. These initiatives should be accessible and mandatory for health care providers.

This study has several limitations. The reliance on an online survey introduces potential selection bias, limiting the generalizability of findings to those engaged in local online communities. The study's exclusion criteria, such as omitting respondents over 45 or those deeming the topic irrelevant, may impact the representation of older BRCA carriers and diverse perspectives on the relevance of pregnancy and breastfeeding. The use of a self-reported survey introduces the possibility of recall bias and subjective interpretations of dissatisfaction. While offering valuable insights, these limitations highlight the need for caution in interpreting and generalizing the study’s findings, emphasizing the importance of addressing these issues in future research. Nevertheless, our study adds valuable insights to the sparse literature addressing explanations and recommendations offered by health practitioners regarding breastfeeding in BRCA carriers. Several disparities with the prevailing guidelines were noted, with an emphasis on the concerning recommendations for discontinuation of breastfeeding. Similar discrepancies may exist in additional countries and regions, suggesting the necessity for further investigation across diverse geographical contexts.

In conclusion, the results of this analysis serve as a clarion call to address the existing disparities in health care recommendations for BRCA carriers, particularly in the context of breastfeeding. The multifaceted implications of these recommendations underscore the need for a systemic shift in health care education and practice. The ultimate goal is to provide the highest quality of care and support to individuals at elevated risk of cancer, helping them make informed decisions that can positively impact their long-term health outcomes.