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Melanie Cole (Host): Welcome to UAB MedCast.

I'm Melanie Cole and joining me today is Dr. Lily Gutnick. She's a Breast Surgeon and an Assistant Professor at UAB Medicine, and she's here to highlight breast cancer in Sub-Saharan Africa. Dr. Gutnick, it's a pleasure to have you with us. I'd like you to start by telling us a little bit about how advanced stage in diagnosis leads to worse outcomes and higher mortalities when it comes to breast cancer. Speak about the prevalence of breast cancer in Sub-Saharan Africa. And is that cancer burden really on the increase?

Lily Gutnik, MD (Guest): Sure. Thank you. Well, first of all, thank you so much for having me here today. It's a privilege and pleasure to be able to speak with you. FIrst of all, Breast cancer is definitely the most common cancer worldwide for all females of all ages. It's actually made up almost about a quarter of new cancers based on our most recent data in 2020.

But when you look at the incidence data, the incidence is higher in higher income countries, including countries in Europe and in the US but unfortunately the mortality is significantly higher in lower income countries and particularly in Sub-Saharan Africa. It is the second leading cause of death after cervical cancer in Sub-Saharan Africa.

And interestingly, when there was research, looking at something called like a case fatality, when you look at the mortality to incidence ratio, for breast cancer in Sub-Saharan Africa, that's about 48%. Right? So basically what it's trying to show is almost half the women that are diagnosed with breast cancer in Sub-Saharan Africa end up dying from it, which is quite different than what we see here in the US and in general, that kind of index or case fatality measure is about four times higher in Sub-Saharan Africa compared to higher income countries like the United States.

So about seventy seven percent of women present in stage three and four disease in sub-Saharan Africa. And going back a little bit more to your question about incidence being on the rise. That is definitely something we are seeing as well. In fact, when we kind of look at graphs from the United States and other similar higher income countries, like in Europe, we see that the incidence has had a flattened curve for the last few years. And fortunately the mortality curve has been going down. But unfortunately in Sub-Saharan Africa, we see our incidence definitely greatly rising, but we also see that mortality curve rising as well.

Host: We'll then based on that, speaking about the characteristics and determinants of this burden, are they clearly ascertained Dr. Gutnick? And do we know the reason for the advanced presentations? Are certain factors such as westernized diet, urbanization, and possibly even increasing awareness. Tell us about this multifactorial increase in reasoning that we're seeing.

Dr. Gutnik: Absolutely. So, I think there's a lot of reasons for why women present at advanced stages. And it's really kind of, think about it in three buckets. There's the biological, social and systemic determinants of health. And then there's reasons for that in all of that. We do see that in Sub-Saharan Africa, women present at younger ages and have more aggressive tumor biology, particularly the triple negative subtype.

And interestingly, when you look at the African-American population in the US you actually do see similar trends compared to Caucasian Americans. And there has been some very interesting sort of genetics and genomics work done comparing women from various countries in Sub-Saharan Africa and African-American populations. And as well as actually similar work being done in Europe with sort of women of African ancestry in European settings compared to various countries in Sub-Saharan Africa. And you do see some commonalities in the genetics and genomics and increasing in more aggressive subtypes, like triple negative.

But I think that's only one factor. There's definitely another huge factor is lack of screening and early detection. There are no organized screening early detection programs, mammography, which is commonly considered standard of care in high resource settings is virtually non-existent.

And then other measures that we know are actually very effective for screening and early detection, such as doing a robust clinical breast exam is also hard to come by in the region as well. And so there's, and then just another really important thing is lack of knowledge and awareness. I mean, people just don't recognize signs and symptoms of breast cancer or brush it off as it being, an infectious complication or other sort of more unfounded reasons.

And unfortunately not only are these misinformation and lack of knowledge and awareness prevalent among community, but unfortunately, a lot of sort of district level providers, also don't really have enough knowledge about breast health. So even if a woman does come in, let's say she notices a lump, right? And she will come to more of the primary health care post. A lot of countries in Sub-Saharan Africa have sort of a tiered healthcare system where there's sort of a primary level, a secondary level and a tertiary level. So let's say they even come at their primary or secondary health posts. A lot of times the clinician there may not recognize that this could be breast cancer and might mismanage it.

And so we actually have data, even systematic review data that shows that, you know, on average in Sub-Saharan Africa from time of symptom recognition by the patient to the time of actual diagnosis is 9 months. Which you could imagine, in the US just as a comparison, that data is something close to about 45 days.

The other interesting finding is that these patients, they will have on average of four contacts with a healthcare provider before actually reaching that true diagnosis. So there's sort of, again, those kind of more systemic issues. And then again, you know, the social issues, there's a lot of fear and stigma around cancer and especially breast cancer, and especially women's health issues and women's cancers.

Unfortunately, there are community beliefs around that this could be related to witchcraft, or this could be related to a wife being promiscuous and therefore she got breast cancer. And unfortunately there's a lot of times with that fear and stigma comes lack of social support. So there's actually, documented in certain countries, really high divorce rate, after women getting diagnosed with breast cancer or having a mastectomy or their husbands and families leaving them. And so not only are they faced with this terrible disease and often advanced stage, which makes it less treatable and less curable, but they also lose their social support. And so again, that fear and stigma of that causes them to then present late. And it turns into this cycle.

Host: Wow. It's really a multifactorial issue and as I'd like you to tell us about your work on understanding these reasons and developing strategies and interventions to address them with an ultimate goal to downstage. As you're telling us about mammography, are there other strategies? Is there evidence of other strategies specifically and particularly in low resource settings and will this rising burden pose any threat to Sub-Saharan Africa's regional development? Speak about your work and this comprehensive really initiative that we're looking at, because it is so multifactorial.

Dr. Gutnik: Absolutely. No, I'm happy to speak about that. So a lot of my current work does kind of focus on the overall long-term goal of downstaging, right, like I mentioned before, 77% of women present in advanced stages three and four, which obviously negatively impacts morbidity and mortality.

And so if the overall goal is to try to downstage them at time of diagnosis, then hopefully we have, a better opportunity for better treatment and for cure. And so a lot of my work focuses on strategies around screening and early detection. I had spent some time and living and working in Malawi, which is a small country in east Africa, where my research was on training lay women to do screening clinical breast exams and breast health education, in an integrated health system approach and it's one of the large tertiary hospitals in the capital city of the country. And basically what my work found was that this is certainly a feasible approach. These lay women could successfully be trained and could develop the skillset and can perform these clinical breast exams as well as physicians can.

And we had a very high acceptance rate among Malawian women of 82% who were really willing and wanted to undergo the service and have the screening done. Among the participants in our study, there was definitely this strong desire for screening and early detection. And there was this basic comprehension that if you catch something when it's early, it will result to better outcomes. So then in 2014, the WHO put out a position paper on mammography, and they basically say that when possible, they recommend an organized screening mammography approach. However, they recognize that this is often not possible in lower resource settings and that opportunistic mammography, meaning, just woman will walk off the street and to get a mammogram because she feels like it isn't really effective overall cancer control prevention strategy.

And so there's been several organizations and expert opinions, that have put forward additional recommendations. The Lancet Commission on Health Equity and Women's Cancers suggested that a clinical breast exam, is cost-effective and feasible. The WHO even endorsed that we're screening mammography is not possible, again, particularly in that organized population-based approach, that clinical breast exams should be explored. The Breast Health Global Initiative, which is an international group of experts, had come forth and put together all sorts of recommendations, guidelines, and pathways, everything from screening, diagnosis, treatment, and survivorship, based on resource availability. So dividing the country's resources based on their basic or moderate or high resource settings and in the basic or lower resource settings, they also recommend the clinical breast exam would be the best modality. And then the most recently is the NCCN, which is the National Comprehensive Cancer Network guidelines, which we actually use in the US as our sort of backbone of guidelines for everything screening and management of all sorts of cancers.

So they in 2018 has started putting forth again, resource stratified guidelines. For their more basic or lower resource settings, they also recommend clinical breast exam as an effective modality. This has been studied in various settings across the world in south America, in India, in various countries in Africa with clinical breast exam being done by nurses, physicians, trained lay women like I did in my study had been done, community health workers, had been used to, and they all basically come to the same conclusion that this is a very feasible and viable approach. I don't think there's any argument that this is an effective intervention. And then very excitingly about a year ago, published in the British Medical Journal was a 20 year followup of a cluster randomized control trial done in India, in urban slums in Mumbai of clinical breast exam screening intervention versus not or surveillance.

Although both groups did get some sort of breast health education upfront, the intervention arm of course then had ongoing screening clinical breast exams that in that case was actually done by community health workers versus the control arm, which was not. And not only did they find a significant down staging of cancers at 20 years of followup, but they actually showed a mortality benefit by almost 30%, particularly for post-menopausal women or women over 50. And so that's our first and only, large randomized clinical trial and long-term data that really shows the effectiveness of this intervention. Since then there's other really cool emerging technologies in this space.

Something called an IBreast, which is kind of physoelectric tool, that's been developed and tested in India and has now been used in various places around the world as well. But again, another more handheld device that could be used by anyone that's trained, of course, including someone like a community health worker or even an imaging technician to perform this exam.

And it identifies, potential areas of the concern, and then knows who to refer for the women for further followup. There's other technology around thermography or, thermolytics, that's also been developed in India and is currently being tested in various parts of the world that takes thermal images of the breast, which again, can be taught and trained how to use the machine by lower, skilled health workers, as another less invasive approach for that screening tool. So I think there's a lot of excitement and a lot of things going on about that. And of course, understanding.

So that's sort of just one aspect on the screening and early detection intervention space, but of course, there's work to be done in just understanding cultural norms and culturally appropriate context and just awareness, education and dispelling myths, which is definitely critical to this mission. As well as of course, educating providers as well, to make sure that, they understand breast health and basic breast health management.

Host: Well, it certainly is. What a great initiative doctor. Thank you so much for joining us today. And a physician can refer a patient to UAB Medicine by calling the mist line at 1-800-UAB-MIST, or you can visit our website at UABmedicine.org/physician. That concludes this episode of UAB Med Cast. For more updates on the latest medical advancements, breakthroughs and research, follow us on your social channels. I'm Melanie Cole.