Knowledge and perceptions of BRCA1/2 genetic testing and needs of diverse women with a personal or family history of breast cancer in South Florida

Abstract

The vast majority of (BRCA1/2) genetic testing has been conducted in White women, in particular Ashkenazi Jewish women, with limited information available for Black and Hispanic women. Understanding perspectives of those who are underserved is critical to developing interventions to support inclusive approaches to genetic testing. This qualitative study explored knowledge and perceptions of BRCA1/2 genetic testing among diverse women in South Florida. We also explored participants’ information needs. Convenience sampling was used to recruit a diverse group of 15 women with a personal or family history of breast cancer. We conducted semi-structured interviews and used grounded theory method to analyze the data. Five themes were identified: (1) lacking awareness and knowledge of BRCA1/2 genetic testing and results among Black women, (2) perceiving BRCA1/2 genetic testing as beneficial to themselves and a way to be proactive about cancer risk, (3) perceiving BRCA1/2 genetic testing as beneficial to family members, (4) interactions with healthcare providers and the healthcare system that shape genetic testing experiences, and (5) information needs for reducing cancer risk and promoting health. Our findings suggest that diverse underserved women perceived genetic testing as beneficial to themselves and family members. Women needed more information about the BRCA genes and genetic testing, prevention strategies, and the latest breast cancer research. Healthcare providers, particularly nurse practitioners, need to engage diverse high-risk women in discussions about their cancer risk, address unmet information needs, and, in particular, educate Black women about the benefits of pursuing genetic testing.

Breast cancer is the most commonly diagnosed cancer after non-melanoma skin cancer and is the second leading cause of cancer death in the USA (American Cancer Society 2020). One major risk factor for developing breast cancer is genetic predisposition (Slavin et al. 2017). Germline pathogenic variants in the BRCA1 or BRCA2 (BRCA1/2) genes account for the majority of hereditary breast cancer susceptibility (Slavin et al. 2017). Additionally, several high and moderate penetrant risk alleles in genes other than BRCA1/2 that confer breast cancer risk have been identified through multigene panel testing (Slavin et al. 2017). Despite tremendous advances made in genetic technology, decreasing costs, media coverage, and increasing access to multigene panel testing, (Roberts and Dusetzina 2017; Scott et al. 2019; Vicuña et al. 2018), germline genetic testing to detect pathogenic variants remains underutilized in the USA, with less than 50% of patients with breast cancer completing genetic testing (Jones et al. 2019; Kurian et al. 2019). Many factors contribute to the underutilization of genetic testing, including patient-level (i.e., awareness, knowledge, attitudes, beliefs, concerns about the misuse of genetic information, and unmet need for genetic literacy) (Hamilton  et al. 2016; Hann et al. 2017; Jones et al. 2017; Vicuña et al. 2018), provider-level (i.e., lack of communication and fewer referrals in minority populations) (Gomez-Trillos et al. 2019; Jagsi et al. 2015; Jones  et al. 2016; McCarthy et al. 2016), and system-level barriers (i.e., insurance coverage and cost of testing) (Scott et al. 2019; Williams et al. 2019). In addition, the limited number of certified genetic counselors (CGCs) and the lack of diversity in the profession have raised concerns regarding limited access to genetic services (Villegas and Haga 2019). According to a recent study, southern states such as Texas, Florida, and Georgia had among the lowest number of practicing genetic counselors per 100,000 population (Villegas and Haga 2019). For example, Florida, which is the second largest state in the South, has 0.26 genetic counselors per 100,000 people, which limits accessibility to genetic services (Villegas and Haga 2019). Although South Florida has a diverse multi-ethnic population, limited data exists on factors affecting completion of genetic testing among diverse high-risk women in this region.

Historically, BRCA1/2 pathogenic variants were most commonly detected among Ashkenazi Jewish women; however, recent studies have reported higher rates of genetic variants in breast cancer susceptibility genes among diverse populations such as Black and Hispanic/Latina high-risk women (Churpek et al. 2015; Jones et al. 2019; Pal et al. 2015; Weitzel et al. 2013). Yet, genetic testing is less likely to occur among racially/ethnically diverse women and individuals of lower socioeconomic status (Bellcross et al. 2013; Halbert et al. 2005; Hall et al. 2009; John et al. 2007; Meiser  et al. 2001), contributing to higher rates of late-stage diagnosis and poorer clinical outcomes in minority compared to non-minority women (Armstrong et al.  2005; Hall and Olopade 2006; Ward and Smith 2010). Among women younger than 45 years old, non-Hispanic Black women have a higher incidence of breast cancer and are twice as likely to be diagnosed with triple-negative breast cancer compared to other racial and ethnic groups (DeSantis et al. 2019). Breast cancer death rates remain 41% higher in Black women than in White women (DeSantis et al. 2019). In addition, breast cancer is the leading cause of cancer death among Hispanic/Latina women, despite lower risk for developing the disease; furthermore, these women are more likely to report an unmet need for discussion of cancer genetics (Gomez-Trillos et al. 2019; Jagsi et al. 2015). Thus, it is essential that high-risk minority women are educated about inherited cancer predisposition and the need for genetic risk assessment in order to improve breast cancer outcomes.

New guidelines from the U.S. Preventive Services Task Force (USPSTF) recommend that primary care providers assess women with a personal or family history of breast, ovarian, tubal, and peritoneal cancer or women with an ancestry associated with (BRCA1/2) pathogenic variants using appropriate risk assessment tools (Owens et al. 2019). In addition, criteria for BRCA1/2 testing by the National Comprehensive Cancer Network (NCCN) have been established since 1998. The guidelines from NCCN qualify individuals for genetic risk assessment and testing based on personal and family history and are frequently updated to broaden the eligibility criteria for multigene panel testing (National Comprehensive Cancer Network (NCCN) 2021). Among women with breast cancer, identifying a pathogenic variant is valuable for both the patient and their family members (Walsh et al. 2017). Genetic testing at the time of cancer diagnosis has several advantages, including targeted treatment with (ADP-ribose) polymerase inhibitors, immunotherapy, and decision-making regarding risk-reducing salpingo-oopherectomy or bilateral mastectomy (Friebel et al. 2019; Offit et al. 2020). In addition, unaffected family members such as sisters and daughters can receive cascade genetic testing, defined as genetic testing in blood relatives of individuals with identified pathogenic variants to learn if they carry the familial pathogenic variant (Walsh et al. 2017). However, the vast majority of information about BRCA1/2 pathogenic variants and risk reduction has been conducted in White women, in particular Ashkenazi Jewish women, with limited acquired data in diverse racial and ethnic groups (Friebel et al. 2019). To fill this critical knowledge gap, we explored knowledge and perceptions of BRCA1/2 genetic testing among Black, Hispanic, and White women with a personal or family history of breast cancer. We also explored participants’ information and support needs for reducing their cancer risk.

Theoretical framework: health promotion model

In this study, Pender’s health promotion model (HPM) was used as a theoretical framework to identify HPM constructs that may emerge from our qualitative analysis. The HPM is one of the most comprehensive models to identify and test factors related to health-promoting behaviors (Alligood 2017; Khodaminasab et al. 2019). The HPM theorizes that people are likely to engage in health-promoting behaviors when significant others, such as family or peers, model the behavior, anticipate the promoting behaviors to occur, and provide support or assistance to perform the behavior (Alligood 2017). The HPM includes three determinants of health-promoting behavior: (a) individual characteristics and experiences (i.e., prior related behavior and personal factors), (b) behavior-specific cognition and affect (i.e., perceived benefits of action, perceived barriers to action, self-efficacy, and interpersonal influences), and (c) behavioral outcomes (i.e., commitment to a plan of action and health-promoting behavior) (Alligood 2017).

Methods

Study design

This was a cross-sectional, exploratory study that used a qualitative approach involving semi-structured interviews in person or over the telephone based on participant’s preference. The study approach was guided by a grounded theory method and investigators hoped findings would guide future work in developing a framework of genetic testing in underserved populations (Charmaz 2014, 2015). Grounded theory methodology is a systematic, flexible qualitative approach that can be used to uncover the beliefs and meanings that underlie action (e.g., use of genetic testing for women with a cancer risk) and captures processes within a social context. We did not intend to develop a theory in this study; instead, we hoped that the findings would guide future work in developing a framework of genetic testing in underserved populations.

Participants

A convenience sample was recruited from the Florida Atlantic University (FAU) Community Health Center (West Palm Beach), the Light of the World Community Health Center (Fort Lauderdale), and the Pink Queen Foundation (West Palm Beach), all located in South Florida. In addition, we utilized a snowballing technique to allow study participants who were already enrolled to invite eligible family members or friends to participate in the study. Eligible participants were as follows: (1) women age 18 years and older with a personal history of breast cancer (preference was given to women diagnosed with breast cancer at age 50 years or younger and Black and Hispanic women to increase the diversity of the study sample); (2) women age 18 years and older with a family history of breast cancer, described as at least one female 1st- or 2nd-degree relative who was previously diagnosed with breast cancer; (3) able to read and speak in English or Spanish; and (4) resided in South Florida. Written informed consent was obtained prior to each interview. Participants were offered a $25 gift card for the time they participated in the study. The Florida Atlantic University (FAU) Institutional Review Board approved this study.

Procedure

The principal investigator (TJ) worked with the clinic staff at the community health centers to recruit patients into the study. The staff screened medical records to identify potentially eligible women and made the initial contact to inform the women about the study. TJ was given the contact information of women who expressed an interest in the study and agreed to be contacted; an invitation letter was mailed to these women. A follow-up phone call was made to the participants who did not respond to the invitation letter. No more than three follow-up telephone contacts, 2 weeks apart, were made to recruit participants. Once contact was initiated, and patients agreed to participate in the study, an appointment was made for an interview in English or Spanish. At the beginning of each interview appointment, the PI reviewed the potential risks and benefits of participating in the study and provided participants with the opportunity to ask questions. Data were collected through a one-time, individual, semi-structured interview conducted in person or over the telephone based on participant’s preference. The PI (TJ), an advanced public health nurse trained in qualitative methods, conducted all interviews in English. A research assistant (SG), a native Spanish speaker, conducted one interview with a Spanish-speaking participant. Interviews were conducted between October 2018 and October 2019 with concurrent data collection and data analysis. When the data reached saturation and no new information emerged, recruitment stopped. Table 1 presents the semi-structured interview guide questions. A resource packet of information about hereditary breast cancer, including a list of genetic counselors in South Florida, was provided to each woman at the end of the interview to avoid bias. Participants completed a demographic information sheet at the end of each interview. All interviews were audio-recorded, transcribed verbatim in English or Spanish by a HIPAA-compliant company, verified, and de-identified prior to analysis.

Table 1.

Semi-structured interview guide questions

Women with a personal history of breast cancer

Women without cancer with a family history of breast cancer

(1) Describe your personal health history and what your health journey has been like? (2) Think backward as far as you can, when was the very first time that cancer came into your mind? • *Tell me about your personal experience with cancer? • *Tell me about your treatment experience? (3) What is your understanding of your future risk for cancer; can you describe what you understand about this? • *What do you think about your risk of cancer recurrence? • *Can you tell me more about what, if anything, you do to reduce your risk of recurrence? (4) Some women are recommended to have genetic testing such as BRCA1/2 testing by getting a blood test to identify their family risk for cancer, tell me what you know about genetic testing? • Have you thought about the benefits of having genetic testing? • Have you ever spoken to a healthcare provider about genetic testing? • What are your intentions for completing genetic testing? (5) Some women who have had genetic testing have shared that they experience barriers or challenges with genetic testing, do you perceive any barriers? • Tell me about any concerns or fears that you may have about BRCA1/2 testing, if any? (6) Tell me about your family members and the ways in which genetic testing could benefit or help them? • Would you share your genetic testing results with your family members? • Would other women in your family be willing to have genetic testing? (7) What are your needs related to reducing your cancer risk and promoting your health? • What information do you need from your doctors or nurses to help you to reduce and manage your breast cancer risk?

(1) Describe your personal health history and what your health journey has been like? (2) Think backward as far as you can, when was the very first time that cancer came into your mind? • *Tell me about your family history of cancer? (3) What is your understanding of your future risk for cancer; can you describe what you understand about this? • *What do you think about your personal risk of developing cancer? • *Can you tell me more about what, if anything, you do to reduce your cancer risk? (4) Some women are recommended to have genetic testing such as BRCA1/2 testing by getting a blood test to identify their family risk for cancer, tell me what you know about genetic testing? • Have you thought about the benefits of having genetic testing? • Have you ever spoken to a healthcare provider about genetic testing? • What are your intentions for completing genetic testing? (5) Some women who have had genetic testing have shared that they experience barriers or challenges with genetic testing, do you perceive any barriers? • Tell me about any concerns or fears that you may have about BRCA1/2 testing, if any? (6) Tell me about your family members and the ways in which genetic testing could benefit or help them? • Would you share your genetic testing results with your family members? • Would other women in your family be willing to have genetic testing? (7) What are your needs related to reducing your cancer risk and promoting your health? • What information do you need from your doctors or nurses to help you to reduce and manage your breast cancer risk?

Data analyses

All transcripts were entered into NVivo 11 for analysis. Spanish audio-recordings were transcribed professionally and translated into English for analysis. To analyze the interview data, we used constant comparative method, which allows for continuous refinement of the findings through coding and thematic analysis (Charmaz 2015). We used a grounded theory approach, which began with open coding in order to examine, compare, and categorize the data, then we used axial coding to make connections between categories, and finally we used selective coding to finalize the themes (Burnard 2006). Each interview transcript was read in its entirety by two authors (TJ and AC). On the second read-through, the authors used open, line-by-line coding to categorize and label the raw data. Codes within and between transcripts were assigned and an initial codebook was developed (Charmaz 2015). A third author (MU) and TJ coded 20% of the transcripts and coding agreement was discussed during team meetings. In addition, using the HPM, a fourth researcher with expertise in qualitative research (HH) assisted with axial and selective coding to ensure trustworthiness and credibility. Descriptive statistics were tabulated with relative frequencies for categorical variables and measures of central tendency for continuous variables (KF).

Results

Participants

The sample included 15 women from South Florida, USA. Of the total sample, four women were family and friends of the participants identified through snowballing; 2 of the participants were relatives’ mother and daughter dyad. Table 2 describes the sample characteristics. The majority of the participants were under the age of 50 years (66.67%) at the time of the interview. The mean age of the participants at the time of the study interview was 43 years (SD, 11.53). The majority of the women had a personal history of a breast cancer diagnosis (n = 13, 86.67%) and their mean age at diagnosis was 41 years (SD = 7.54). The median number of years since diagnosis was 2 (range: 0.5–13 years) prior to the interview. The sample was racially/ethnically diverse with 11 (73.33%) women identifying as Black/African American and 4 (26.67%) women identifying as White. Regarding ethnicity, 2 (13.33%) of the White women identified as Hispanic/Latina and 1 identified as Ashkenazi Jewish. About half of the participants were college graduates (46.67%). The majority of the participants were married, partnered, or living together (53.33%) and working full-time (53.33%). Of the participants who disclosed an annual household income (n = 14), 7 (50%) of the participants earned less than $50,000 per year and most reported at least some level of difficulty paying family bills (60%). Eight participants reported completing BRCA1/2 or multigene panel testing (53.33%). Of these women, seven reported negative genetic test results and one woman reported being BRCA1 positive.

Table 2.

Sample characteristics (n = 15)

Characteristics	n	%
Age at presentation in years (mean, SD, range)	43 (11.53) [min, max]
Age at presentation in years
≤50	10	66.67
>50	5	33.33
Age at diagnosis in years (mean, SD, range)	41 (7.54) [24, 54]
Age at diagnosis in years
≤50	12	92.31
>50	1	7.69
Years since diagnosis	2 [range: 0.5–13]
Ethnicity
Hispanic/Latino	2	13.33
Non-Hispanic	13	86.67
Race
Black/African American	11	73.33
White	4	26.67
Education
High school diploma or G.E.D.	3	20.00
Some college, business, or technical school	4	26.67
College graduate	7	46.67
Post-graduate degree	1	6.66
Insurance
Private	7	46.67
Public	7	46.67
Uninsured	1	6.66
Marital status
Married, partnered, or living together	8	53.33
Separated, divorced, or widowed	3	20.00
Single, never married	4	26.67
Work status
n	2	13.33
Working full-time	8	53.34
Working part-time/student	3	20.00
Unemployed	2	13.33
Annual household income
< $5000	2	14.29
$5000 to $11,999	3	21.43
$12,000 to $15,999	1	7.14
$16,000 to $24,999	0	0.00
$25,000 to $49,999	1	7.14
$50,000 or more	7	50.00
Difficulty paying family bills
Not difficult at all	6	40.00
Somewhat difficult	3	20.00
Very difficult	5	33.33
Extremely difficult	1	6.67
Personal history of breast cancer
Yes	13	86.67
No	2	13.33
Completion of genetic testing
Yes	8	53.33
No	7	46.67

Overview

Five themes were identified: (1) lacking awareness and knowledge of BRCA1/2 genetic testing and results among Black women, (2) perceiving BRCA1/2 genetic testing as beneficial to themselves and a way to be proactive about cancer risk, (3) perceiving BRCA1/2 genetic testing as beneficial to family members, (4) interactions with healthcare providers (HCPs) and the healthcare system that shape genetic testing experiences, and (5) information and support needs for reducing cancer risk and promoting health. Table 3 presents the findings with HPM constructs that emerged and exemplar quotations and the results are discussed below.

Table 3.

Qualitative themes and exemplar quotes

Theme 1: Lacking awareness and knowledge of BRCA1/2 genetic testing and results among Black women (n = 10)	(Participant #2: Black female with a personal history of breast cancer diagnosed at age 41 years): “[Doctor #2] explained it. You know, at first, I was like, ‘what are you trying to say? Are you saying that it comes from a family history? Or what is genetic testing?’ Because I really had no idea that you can do this type of testing.”
	(Participant #4: Black female with a family history of breast cancer): “I get nervous about my data being collected and possibly going to the wrong source. Will it get stored in a database that others can use for research or that others can possibly sell?”
	(Participant #7: Black female with a personal history of breast cancer diagnosed at age 34 years): (I: Prior to your diagnosis, what did you think of genetic testing?) “No, I was not aware of it. It was a nurse practitioner. She explained that when they did the test they could do it either two ways. Either by using your saliva or blood. She explained all that. She explained that genetic testing kind of helps you to get an idea of what your risk would be like, if it was something that you could pass on to your children. And they test for I think, 26 different genes. All of them came back negative.”
Health promotion model construct: perceived benefit of action
Theme 2: Perceiving BRCA1/2 genetic testing as beneficial to themselves and a way to be proactive about cancer risk (n = 13)	(Participant #5: White female with a personal history of breast cancer diagnosed at age 45 years): “But yet, there’s the few that do not have any family of history of it, for example, myself and that in a couple of other people that I’ve spoken with as well. So that, to me, is very bizarre. I feel like it should be part of your woman wellness exam because we are going to do mammograms, we are going to do, you know, your pelvic exams, like, why would you not include that to be proactive?”
	(Participant#9: Black female with a personal history of breast cancer diagnosed at age 45 years): “The greatest thing is to know...Because knowledge is power. So when you know something [genetic testing results], then you know how to work with it or work around it…I just stay positive. And I just tell the doctors, Do whatever you have to do.”
	(Participant #14: Hispanic female with a personal history of breast cancer diagnosed at age 38 years): “Its [genetic testing] something very simple, because it is done through blood tests. It is not something from the other world; I liked it because they do tests on various types of genes. So, it’s already a way of, ruling things out. I do not remember if there were 36 or 40, something like that, types of genes that they tested through that blood sample, she told me. In my case, they told me it was negative.”
Theme 3: Perceiving BRCA1/2 genetic testing as beneficial to family members (n = 8)	(Participant #1: Black female with a family history of breast cancer): (Tell me what you think about genetic testing? What have you heard, and what do you think about it?). “It’s good, because when my daughter was diagnosed with breast cancer at age 25, she was upset with me for about two and a half years going through that, because she blamed me. She said I’m the one who gave it to her. I gave her cancer…“So, I guess, for my oncologist, to ease my mind [about if it runs in the family], she sent me to [Hospital #1], at the other cancer center, and they did, I think it was the BRCA1.”
	(Participant #2: Black female with a personal history of breast cancer diagnosed at age 41 years): “But for one reason that sticks to my mind is, I have daughters…So to them, when they heard of genetic testing, they were like, ‘Mama, you need to do this. We need you to do this so we’ll know if we are, at risk for, you know, getting the same diagnosis that you have.’”
	(Participant #5: White female with a personal history of breast cancer diagnosed at age 45 years): “But if that BRCA gene does come back and that’s something to be aware of, then I have to show that with her [daughter] and then know at what point, at what age, that she would be allowed to get that testing done as well.”
Health promotion model construct: interpersonal influence
Theme 4: Interactions with healthcare providers and the healthcare system that shape genetic testing experiences (n = 13)	Received a recommendation for genetic testing
	(Participant #7: Black female with a personal history of breast cancer diagnosed at age 34 years): “She was very good, a nurse practitioner. She explained that when they did the test they could do it either two ways. Either by using your saliva or blood. She explained all that. She explained that genetic testing kind of helps you to get an idea of what your risk would be like, if it was something that you could pass on to your children. And, they test for like, I think, 26 different, genes. All of them came back negative. But it was a good experience.”
	(Participant #8: White female with personal history of breast cancer diagnosed at age 35 years who is BRCA1 positive): “Sure. So I was diagnosed as BRCA1 positive in 2009. The reason I was tested was my mom, my mother was diagnosed with breast cancer at the age of 45 and my mother’s cousin was also diagnosed with breast and ovarian cancer, so my primary care sent me to a genetic specialist. It was indicated to test for BRCA, and I tested positive in 2009… I think I appreciated the screenings because it made me feel safer. I did know that the best next move would be to do a preventative mastectomy. I knew it was coming based on my conversations with my genetic physician and another specialist I consulted with but I kept putting it off. I thought I could do it in my 40s and I would still have time to have children first.”
	(Participant #14: Hispanic female with a personal history of breast cancer diagnosed at age 38 years): “I did not ask if the person who was doing it to me was the genetic counselor. She gave me a brochure--where she said all the tests they checked with the blood. I do not remember if there were 36 or 40, something like that, types of, of genes that they tested through that blood sample, she told me. In my case, they told me it was negative. But despite the fact that it had been negative, as I said before, my sisters and my mother still have a high percentage in which they could develop it. So, the recommendation was that their mammograms should be done even if they were not of age.”
	Received no recommendation for genetic testing
	(Participant #3: Black female with a personal history of breast cancer diagnosed at age 48 years): (I: Can you recall if you have had any conversations or discussions with your – either doctors or nurses – uh, about having genetic testing?) “No, I have not.” (I: So to your knowledge, no one has recommended that you had – or as an option for you to have – genetic testing. Is that correct?) “Yeah, that’s correct.”
	(Participant #5: White female with a personal history of breast cancer diagnosed at age 45 years): “Now, the flip side of this really bothers me because I asked the medical oncologist that I was assigned to, who’s also the same one that told me there’s absolutely no way this could be part of IVF, said no, I do not need to get that [genetic testing] because I do not have any family history of it…So I still do not know if I should be getting the BRCA testing or not, or I do not know.”
	(Participant #6: Black female with a personal history of breast cancer diagnosed at age 54 years]: (I: Okay. Um, is this something that you ever discussed with your doctor, like, especially after you were diagnosed with breast cancer?) “No. Hmm-mm. (I: Has any one of your providers brought up genetic testing to you at all?) “No. Hmm-mm. No.”
	Healthcare system (financial)
	(Participant #8: White female with personal history of breast cancer diagnosed at age 35 years who is BRCA1 positive): “Back then, the insurance could still penalize you for your results, which they cannot today, I believe. I did it privately through a service on my own and paid out of pocket. And it was expensive back then but well worth it, I was surprised when it came back positive.”
	(Participant #10: Black female with a personal history of breast cancer diagnosed at age 24 years): “When I got diagnosed, they sent me for the genetic testing. And at first, my insurance wasn’t going to pay for it, and then they came back and said my insurance was going to pay for it. When the results came back they did not find anything genetic.”
	(Participant #15: Hispanic female with a personal history of breast cancer diagnosed at age 44 years): “It’s now more common than it was then when I was diagnosed. Unfortunately, at the time of my diagnosis, because I could not show that immediate pedigree-- my grandmother, grandfathers, or aunts, uncles, immediate-- you know brother or sister. It was out of price range for me.”
Theme 5: Information and support needs for reducing cancer risk and promoting health (n = 15)	(Participant #5: White female with a personal history of breast cancer diagnosed at age 45 years): “I want to know about the BRCA gene. I would like to know at what point I am completely cancer-free. I would like to know who I’m supposed to follow-up with and how often. Like, I do not know any of this stuff.”
	(Participant #7: Black female with a personal history of breast cancer diagnosed at age 34 years): “I think that in my case because it’s triple negative and a lot of people make the comment that, triple negative is more aggressive--So I want-- I do not want to get, like, the typical textbook answer, but I’m hoping that I can find, like, another oncologist after I do my procedure. Somebody who is more into research, who is willing to do it on a patient-to-patient basis and not just a general basis, “Okay. You’re triple negative, we’ll go with chemo,” and just throw that at you. I would prefer to go with somebody who would even say, “You know, maybe you can eat certain foods, a higher content of certain foods that is anti-cancerous or helps to fight cancer.” That kind of information would be very valuable to me.”
	(Participant #8: White female with personal history of breast cancer diagnosed at age 35 years who is BRCA1 positive): “Fertility is a huge thing for information for me. I do see my oncologist a lot for the anxiety…When you go through chemo, they throw drugs at you. There are like, different drugs to deal with this symptom, this symptom, but you have to then go back to your life. And a lot of the anxieties do not go away or a lot of the symptoms. So, definitely medication management is something that’s huge.”

Theme 1: Lacking awareness and knowledge of BRCA1/2 genetic testing and results among Black women

A key barrier that the majority of the Black participants reported was a lack of awareness and knowledge about BRCA1/2 genetic testing and the meaning of their results. Several Black women explained that prior to their breast cancer diagnosis, they had never heard of BRCA1/2 genetic testing. Participants shared the following:

[My doctor] explained it. You know, at first, I was like, "what are you trying to say? Are you saying that it comes from a family history? Or what is genetic testing?" Because I really had no idea that you can do this type of testing [Participant #2: Black female with a personal history of breast cancer diagnosed at age 41].

[I: Prior to your diagnosis, what did you think of genetic testing?] No, I was not aware of it. It was a nurse practitioner. She explained that when they did the test they could do it either two ways. Either by using your saliva or blood. She explained all that. She explained that genetic testing kind of helps you to get an idea of what your risk would be like, if it was something that you could pass on to your children. And they test for I think, 26 different genes. All of them came back negative. [Participant #7: Black female with a personal history of breast cancer diagnosed at age 34].

And it's something that's not really discussed and mentioned, because I've never heard of genetic testing until after the cancer diagnosis. So, I think it would be something good, educational wise [Participant #13: Black female with a personal history of breast cancer diagnosed at age 37].

One woman [participant #1] with a strong family history of breast cancer lacked knowledge of genetic testing and explained that she did not quite understand the results:

The gene that I do have, she said that all the male kids are carriers and all the daughters, all the female will get breast cancer, from whatever tests she did. However, I didn't quite understand it [Participant #1: Black female with a family history of breast cancer].

One woman who was diagnosed with breast cancer at age 42 years and had not yet completed genetic testing explained that she had never heard of BRCA testing despite her age at diagnosis and also reported that her mother died of breast cancer:

[I: Okay. Have you heard of BRCA testing?] No, Nuh-uh. [I: Any of your healthcare providers have spoken to you about genetic testing?] No. Because I guess they knew about my mom dying of breast cancer so I don't know [Participant #11: Black female with a personal history of breast cancer diagnosed at age 42].

Two women had misconceptions about the genetic testing process. One felt that completing BRCA1/2 genetic testing would hinder her kids from getting health insurance. The other woman was nervous about her genetic data being collected and misused:

What do I know? Well, I know what I was told several, several years ago. I can't remember by who but, but somebody told me. Uh, that if you get that done, it can also hinder as your kids get older, them getting health insurance [Participant #6: Black female with a personal history of breast cancer diagnosed at age 54].

I get nervous about my data being collected and possibly going to the wrong source. Will it get stored in a database that others can use for research or that others can possibly sell? [Participant #4: Black female with a family history of breast cancer].

Theme 2: Perceiving BRCA1/2 genetic testing as beneficial to themselves and a way to be proactive about cancer risk

Despite several knowledge gaps, the majority of the women described perceiving BRCA1/2 genetic testing as beneficial for themselves and as a way to be proactive about their cancer risk. Genetic testing could provide information about the cause of their cancer or knowledge of whether or not cancer runs in the family. In addition, the women shared that receiving their genetic test results would allow them to rule out hereditary cancer risk and to take care of things ahead of time, meaning detecting cancer early. One woman shared:

Oh sure, there’s lots of benefits. You’d be able to maybe- I don’t know- take care of things ahead of time. [Participant #6: Black female with a personal history of breast cancer diagnosed at age 54].

Another woman who was diagnosed with breast cancer at age 41 years who completed BRCA1/2 genetic testing explained the following when asked about her beliefs of genetic testing:

From what I've learned, I favor it for, for so many reasons… I support the genetic testing. I think it's a good thing that they've come up with [Participant #2: Black female with a personal history of breast cancer diagnosed at age 41].

While majority of the women were diagnosed with breast cancer at a young age, 50 years and younger, some reported that they did not complete genetic testing at the time of diagnosis. Of the women who did not complete genetic testing, several viewed the test as beneficial and showed an interest when prompted to discuss their perceptions of BRCA1/2 genetic testing. One woman who was diagnosed with breast cancer at age 45 years and had no family history of the disease felt like BRCA1/2 genetic testing should be a part of the women’s wellness exam, since most women who are diagnosed with breast cancer do not have a family history of the disease (Shiyanbola et al. 2017):

But yet, there's the few that do not have any family of history of it, for example, myself and that in a couple of other people that I've spoken with as well. So that, to me, is very bizarre. I feel like it should be part of your woman wellness exam and—because we're going to do mammograms, we're going to do, you know, your pelvic exams, why would you not include that [genetic testing] -- to be proactive? [Participant #5: White female with a personal history of breast cancer diagnosed at age 45].

One woman who did not complete genetic testing at the time of her breast cancer diagnosis explained the following:

[I: What are your thoughts about sitting down with a genetic counselor now, today, and revisiting the idea of genetic testing?] Whether insurance would pay for it, and if they didn't, what the cost would be. I would be receptive to it [Participant #15: Hispanic female with a personal history of breast cancer diagnosed at age 44].

Another woman with a family history of breast cancer who had not yet completed genetic testing was ready to complete the test on the day of the interview. She shared the following:

Before I actually did this interview with you and I was talking to the research assistant, I had thought that I was actually going to get my blood drawn today and get my genetic testing. So I was super excited because I felt that that's a really important step for me [Participant #4: Black female with a family history of breast cancer].

Theme 3: Perceiving BRCA1/2 genetic testing as beneficial to family members

Some women recognized that the decision to have genetic testing extended beyond an individual benefit to family members. Concern for family members, particularly children and siblings, emerged as important among the women. Once the women complete genetic testing and receive their results, this information could be passed on to family members who could be alerted to complete mammograms at an earlier age, if necessary. Knowing at what age daughters should receive genetic testing themselves was a priority for some women. The women were aware of the hereditary nature of breast cancer and explained that their family members can develop cancer also; therefore, genetic testing could inform them of the need for earlier screenings. One woman shared that her children motivated her to complete genetic testing:

So to them, when they heard of genetic testing, they said, Mama, you need to do this. We need you to do this so we'll know if we're, at risk for, you know, getting the same diagnosis you have [Participant #2: Black female with a personal history of breast cancer diagnosed at age 41].

Genetic testing was viewed as a life-saving test for one woman and her family members; she explained that instead of being ashamed and withholding information from her family and having them develop cancer, she would share information about genetic testing with family members, which could save their lives:

How can you be so ashamed of something, and you could save your family? You know? And they die. They die of the disease, they don't get treated, and then they turn around and maybe your daughter, all these other people, they develop the cancer. So no, I would never withhold anything like that from her-- from them [Participant #13: Black female with a personal history of breast cancer diagnosed at age 37].

Two women described the impact of genetic testing on siblings. One woman who was of Ashkenazi Jewish descent was found to be BRCA1 positive and later diagnosed with breast cancer at age 35 years explained the importance of familial genetic testing as her brother and sister completed their own genetic testing, which came back negative. Another woman who was diagnosed with breast cancer at age 34 years shared that completing BRCA1/2 genetic testing and receiving a negative result was reassuring for her sisters:

I think it's actually good because at least it can inform your family members. For me, I have sisters in similar age groups to me. So after me doing genetic testing, knowing that it came back-- that it's not genetic gave me a sigh of relief for them [Participant #7: Black female with a personal history of breast cancer diagnosed at age 34].

Theme 4: Interactions with healthcare providers and the healthcare system that shape genetic testing experiences

The majority of women recognized the role of their healthcare provider in facilitating the process of having genetic testing. Women shared both positive and negative interactions with their providers that influenced them completing BRCA1/2 genetic testing. Five women shared that they did not recall having conversations with a healthcare provider about having BRCA1/2 genetic testing despite a diagnosis of breast cancer. Participants shared the following:

Now, the flip side of this really bothers me because I asked the medical oncologist that I was assigned to, who’s also the same one that told me there’s absolutely no way this could be part of IVF, said no, I don’t need to get that [genetic testing] because I don’t have any family history of it [Participant #5: White female with a personal history of breast cancer diagnosed at age 45].

[I: -- were you told about genetic testing once you were diagnosed?] No. Nuh-uh.” [I: No. So, just to clarify, any of your healthcare providers have spoken to you yet about genetic testing?] “No.” [Participant #11: Black female with a personal history of breast cancer diagnosed at age 42].

[I: Can you recall if you’ve had any conversations or discussions with your – either doctors or nurses—uh, about having genetic testing?] No, I haven’t.” [I: So to your knowledge, no one has recommended that you had – or as an option for you to have genetic testing. Is that correct?] “Yeah, that’s correct [Participant #3: Black female with a personal history of breast cancer diagnosed at age 48].

In contrast, eight women reported that their providers played a positive role in their completion of BRCA1/2 genetic testing. These women reported having discussions with their healthcare providers about having BRCA1/2 genetic testing. One woman explained that the nurse practitioner (NP) ordered the genetic test and explained that it could be completed either using blood or saliva. Participant #8 explained that her primary care provider sent her to a genetic specialist after her mom was diagnosed with breast cancer at age 45 years and her cousin was diagnosed with ovarian cancer. This participant’s BRCA1/2 genetic testing results revealed that she had a pathogenic variant in the BRCA1 gene. Although she discussed the possibility of having preventative mastectomy with her provider, she delayed this decision as she thought that she had additional time before developing cancer and wanted to have children first. However, she was subsequently diagnosed with breast cancer at age 35 years:

Sure. So I was diagnosed as BRCA1 positive in 2009. The reason I was tested was my mom, my mother was diagnosed with breast cancer at the age of 45 and my mother's cousin was also diagnosed with breast and ovarian cancer, so my primary care sent me to a genetic specialist. It was indicated to test for BRCA, and I tested positive in 2009… I think I appreciated the screenings because it made me feel safer. I did know that the best next move would be to do a preventative mastectomy. I knew it was coming based on my conversations with my genetic physician and another specialist I consulted with but I kept putting it off. I thought I could do it in my 40s and I would still have time to have children first [Participant #8: White female with personal history of breast cancer diagnosed at age 35 who is BRCA1 positive].

Another participant explained that while she was not aware of BRCA1/2 genetic testing prior to her diagnosis, once she discussed it with her doctor, she became supportive of having genetic testing:

Yeah. So, I guess, for my oncologist, to ease my mind, she sent me to [Hospital #1], at the other cancer center, and they did, um I think it was the BRCA1, but they said it didn't-- she didn't find anything [Participant #1: Black female with a family history of breast cancer].

Other participants shared the following:

So once I read into it and talked with my doctor about it, who really supports genetic testing, I knew that it was something that I would support. Because, you know, for so long breast cancer patients or any other patient that received the diagnosis of cancer, their treatments were all the same [Participant #2: Black female with a personal history of breast cancer diagnosed at age 41].

Oh, she was very good. It was, a nurse practitioner. She explained that when they did the test they could do it either two ways. Either by using your saliva or blood. She explained all that [Participant #7: Black female with a personal history of breast cancer diagnosed at age 34].

A few women reported financial barriers to completing genetic testing, including lack of insurance, insurance delays, test not being covered by insurance, and high out-of-pocket costs. The women voiced concerns about genetic testing cost at the time of their diagnosis several years ago. Women shared the following:

[I: Some of the difficulties that women have shared is with not having good insurance coverage or sort of being concerned about the test itself. Do you have any concerns that you would like to share?] Maybe the insurance part. I lost my husband, so that took a lot away. I had to get some insurance on my own. Well, I signed up for some. I can't use it until next month [Participant #3: Black female with a personal history of breast cancer diagnosed at age 48].

Back then, the insurance could still penalize you for your results, which they can't today, I believe. I did it privately through a service on my own and paid out of pocket. And it was expensive back then but well worth it, I was surprised when it came back positive [Participant #8: White female with personal history of breast cancer diagnosed at age 35 who is BRCA1 positive].

It's now more common than it was then when I was diagnosed. Unfortunately, at the time of my diagnosis, because I could not show that immediate pedigree-- my grandmother, grandfathers, or aunts, uncles, immediate-- you know brother or sister. It was out of price range for me [Participant #15: Hispanic female with a personal history of breast cancer diagnosed at age 44].

Theme 5: Information and support needs for reducing cancer risk and promoting health

Participants described needs related to health promotion and reducing cancer risk. Three respondents wanted to be made aware primarily of the latest research on breast and ovarian cancers. One participant who was diagnosed with triple-negative breast cancer stated that due to the aggressive nature of triple-negative breast cancer, she would like to find an oncologist who can assist her with learning about certain foods to eat that are anti-cancerous. Two women wanted more information about the BRCA gene and genetic testing. Other areas of information needs related to with whom to follow up and when, prevention strategies such as what to eat and recommended exercises, fertility, medication management, a request to be heard by doctors due to young age at diagnosis, surgical options such as mastectomy vs. lumpectomy, and additional testing to learn about for prevention because mammograms are not recommended post mastectomy. A few women did not express any needs. Participants shared the following:

I want to know about the BRCA gene. I would like to know at what point I am completely cancer-free. I would like to know who I'm supposed to follow-up with and how often. Like, I don't know any of this stuff [Participant #5: White female with a personal history of breast cancer diagnosed at age 45].

Just any additional testing or resources to know. I cannot get mammograms. I do not have that. So without going through a whole PET scan, is there anything else I need to do? Doing a bone density. Doing annual paps. You know, is there anything else I could do because of my breast cancer, which I know that I am at higher risk now for ovarian cancer [Participant #15: Hispanic female with a personal history of breast cancer diagnosed at age 44].

Any information that may come, that can be productive for me, like: "Well, this is what I should do, this is what I should not do," is more than welcome, because one really ignores many situations with this cancer. One does not have information about this disease until one is already in the situation [Participant #14: Hispanic female with a personal history of breast cancer diagnosed at age 38].

Discussion

This qualitative study provides insights into the knowledge and perceptions of BRCA1/2 genetic testing among diverse women with a personal or family history of breast cancer who reside in South Florida. We found that Black women had low awareness and knowledge of BRCA1/2 genetic testing, including not being aware that BRCA testing existed prior to their breast cancer diagnosis, not knowing about BRCA testing at the time of the interview, confusion about the meaning of genetic test results, and misconceptions about the security of genetic data and potential insurance discrimination implications. The knowledge gap about genetic testing did not appear for Hispanic or White women. These results are consistent with prior studies that have found significant differences in awareness and knowledge of BRCA1/2 testing among Black and White women (Rubinsak et al. 2019; Suther and Kiros 2009) and limited knowledge regarding genetic testing specifically among Black women (Adams et al. 2015; Hurtado-de-Mendoza et al. 2017; Sheppard et al. 2014; Thompson et al. 2002). In an anonymous study of 301 women with a personal or family history of breast and/or ovarian cancer at a single academic institution, interest in genetic testing was the same between racial groups, but Black and Hispanic women were less likely to have awareness about genetic testing compared to White women (Rubinsak et al. 2019). In an intercept study conducted with 50 Black women in public spaces, 88% of the women had never heard of BRCA1/2 genes (Adams et al. 2015). This knowledge gap will likely contribute to lower utilization of genetic testing among Black women compared to other racial and ethnic groups and could possibly widen the disparity gap.

Perceived benefits to action, a construct of the HPM, was an important finding in this study. The majority of the participants perceived BRCA1/2 genetic testing as beneficial to themselves and family members, as genetic testing could provide information about the cause of their cancer and allow them to engage in prevention strategies. Participants described that the benefits of genetic testing extend beyond the individual to family members. Some women were aware of the hereditary nature of breast cancer and explained that genetic testing could inform their family members of the need for earlier screenings. One woman of Ashkenazi Jewish descent, who was found to be BRCA1 positive and later diagnosed with breast cancer, explained the importance of familial genetic testing as several of her family members underwent testing. Recent efforts have been extended to at-risk family members of individuals who carry a pathogenic BRCA1/2 variant or other breast cancer susceptibility genes through cascade genetic testing (Frey et al. 2020).

In our sample, a little more than half of the women (53.33%) reported completing BRCA1/2 genetic testing or multigene panel testing, and one participant of Ashkenazi Jewish decent reported that she was BRCA1 positive. Genetic testing rates in high-risk populations have been previously reported at less than 50% completion, and frequency of pathogenic variants ranges from 7 to 27% (Jones et al. 2019; Kurian et al. 2019; Scott et al. 2019). Genetic testing is particularly important for minority women because a vast majority of the information about pathogenic variants in breast and ovarian cancer susceptibility genes have been collected among White and Ashkenazi Jewish women (Seven et al. 2020). Knowledge of genetic risk is valuable because it can lead to risk-reducing strategies, ultimately saving lives and reducing disparities in breast cancer mortality (Seven et al. 2020). The National Comprehensive Cancer Network (NCCN) offers testing criteria for high penetrance breast and ovarian cancer susceptibility genes, including BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53, for individuals with cancer or a family history of cancers that meet criteria. It is vital that healthcare providers are familiar with these recommendations (National Comprehensive Cancer Network (NCCN) 2021).

According to the HPM, healthcare providers, such as nurses, constitute a part of the interpersonal environment, which exerts influence on patients that can increase or decrease their commitment to and engagement in a health-promoting behavior such as completing genetic testing to manage breast cancer risk (Alligood 2017). We found that participants described the essential role of interactions with their healthcare providers as shaping their genetic testing experience. Providers were viewed as an important source of information, support, and guidance throughout the genetic testing process. Eight participants reported having a discussion with a healthcare provider about having genetic testing. One participant, a Black female who was diagnosed with breast cancer at age 34 years, shared that she had a positive experience with her nurse practitioner who explained that the test could either be done with blood or saliva and discussed the benefits of testing. Another participant, a Hispanic female with a personal history of breast cancer diagnosed at age 38 years, explained that she was given a brochure at the time of testing that explained the number of genes tested and the process. These findings are especially important because previous studies have confirmed that having discussions with a healthcare provider and receiving a referral to pursue testing are major facilitators of completion of genetic testing (Cragun et al. 2015; Jagsi et al. 2015). Although genetic testing discussions occurred between the majority of women and their healthcare providers, seven women shared that they neither discuss genetic testing nor receive a referral for testing from a healthcare provider. These findings are consistent with studies that have found that genetic testing is less likely to occur without a provider recommendation (Jones et al. 2017; Kurian et al. 2017; McCarthy et al. 2016; Scott et al. 2019). Understanding perspectives of those who are underserved is critical to developing interventions to support inclusive approaches to genetic testing.

Notably, a few of our participants reported financial concerns as a barrier to obtaining genetic testing such as lack of insurance, insurance delays, testing not being covered by insurance, and high out-of-pocket costs. Although most types of insurance cover the cost of BRCA1/2 testing for individuals who meet guideline criteria, many patients still incur out-of-pocket expenses associated with genetic testing and downstream services following a positive test result (Rubinsak et al. 2019). In our sample, the median number of years since diagnosis was 2 years prior to the interview. For some women, cost associated with genetic testing could have been a barrier at the time of their diagnosis as 50% percent of the participants reported incomes ≤$50,000 per year and 60% reported difficulty paying family bills, reflecting an economic health disparity. To our knowledge, all women in this study met criteria for genetic testing based on age at diagnosis or family history and should have discussed their genetic risk with a healthcare provider. Since 2013, the cost of genetic testing has reduced tremendously due to the case of Association for Molecular Pathology v. Myriad Genetics, in which the US Supreme Court ruled unanimously that naturally occurring DNA was a product of nature and not patent eligible (Jones et al. 2019). Additionally, many genetic testing laboratories offer financial assistance and economic hardship programs for uninsured and underinsured individuals (Hayden et al. 2017). It is important for laboratories to increase awareness about the potential assistance resource.

Implications for practice

It is critical that healthcare providers, particularly nurse practitioners (NPs), engage in discussions with diverse high-risk women about their cancer risk and educate them about the importance of pursuing genetic testing to detect pathogenic variants in BRCA1/2 and other breast cancer susceptibility genes. NPs should be educated about the role of genetic testing in facilitating precision health and be prepared to offer genetic testing resources to underserved populations. NPs should also be aware of the unmet information needs of women with a personal or family history of breast cancer, including information about BRCA1/2 genes and genetic testing; prevention strategies, including appropriate foods to eat and appropriate exercises; follow-up cancer care; surgical options such as mastectomy vs. lumpectomy; fertility; medication management; and the latest research related to breast and ovarian cancer. Our study has demonstrated that diverse women perceive genetic testing to be beneficial to themselves and their family members, particularly their daughters and their sisters. Evidence has shown that women’s attitudes toward genetic testing are generally positive with perceived benefits being related to personal health and family (Hann et al. 2017). Future studies should focus on developing interventions to address the knowledge gaps including preventive strategies to promote health in themselves and their families. NPs should encourage the use of decisional support tools to empower and activate patients and their providers to engage in shared decision-making about genetic counseling and testing, with emphasis on cancer risk reduction.

As primary care providers and oncology specialists, NPs are on the frontline and are best poised to engage diverse high-risk women in genetic risk assessment and multigene panel testing. NPs often work in primary care settings such as community health centers, high-risk genetics clinics, and retail clinics (e.g., minute clinics) and have access to a diverse group of high-risk women. It is imperative that NPs use the NCCN guidelines to routinely screen high-risk women for genetic red flags and navigate them through genetic counseling and testing. In our study, participants spoke of their interactions with oncology specialists including nurse practitioners, indicating their vital role in detecting hereditary cancers. Given our findings that Black women demonstrate low awareness of genetic testing, it is imperative that NPs continue to screen high-risk Black women and keep them on their radar to target them for genetic counseling and testing when appropriate. There are benefits to activating NPs as healthcare providers (HCPs) with whom high-risk women should consult for genetics. However, evidence shows that NPs experience lack of knowledge and low confidence in incorporating genetics into practice (Cox et al. 2012; Smania 2016), indicating the need for NPs to access available educational tools and resources to enhance their practice in genetic counseling and testing (Silverman et al. 2018; Smania 2016; Tonkin et al. 2020).

Nurse practitioners work from a caring holistic framework; therefore, they are well equipped to address the psychosocial needs of high-risk women prior to and after genetic testing. With the expansion of multigene panel testing and the uncertainty surrounding genetic testing results, each patient will present with their unique individual psychosocial needs. It is particularly important for NPs to screen high-risk women with mental illness to address anxiety that may be caused by the genetic testing process (Jones et al. 2020). NPs are well suited to support women by providing anticipatory guidance throughout the entire genetic testing process and making referral to appropriate specialists based on the identified needs of high-risk women. We envision NPs working independently to provide pre-test genetic counseling, possibly ordering their own genetic testing within their clinic or office, providing disclosure of genetic testing results and post-test counseling, and collaborating with licensed genetic counselors and medical geneticists as complex cases emerge.

Limitations

Our study has some limitations. First, we included a sample with a majority of Black women and 4 White participants, 2 of whom were Hispanic, and 1 Ashkenazi Jewish woman. The study participants may not be representative of the larger population of diverse high-risk women. However, since we recruited from two community health centers, a breast cancer community organization, and through snowballing, results may be more generalizable than recruiting from one location only. Second, several of the participants were diagnosed with breast cancer at least 5 years earlier, which can introduce possible recall bias. We believe that all women in this study met the criteria for genetic counseling/testing based on age at diagnosis and family history; however, this was not confirmed by medical record and is beyond the scope of this study. Third, although the data were collected through self-report and could not be verified, we interviewed until the point of saturation of themes.

Conclusion

The majority of the participants perceived BRCA1/2 genetic testing to be beneficial to themselves and family members. Participants generally reported that their interactions with healthcare providers and the healthcare system shaped their genetic testing experiences. Healthcare providers, particularly nurse practitioners, need to engage diverse high-risk women in discussions about their cancer risk, address unmet information and support needs, and, in particular, educate Black women about the benefits of pursuing genetic testing.

Funding

This study was funded by the DAISY Foundation Grant # JPB-2016-57-A.

Declarations

Ethics approval and consent to participate

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki 1964 and its later amendments or comparable ethical standards.

This article does not contain any studies with animals performed by any of the authors.

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare no conflict of interest.