Breast cancer is the most common malignancy worldwide, with highest mortality in sub-Saharan Africa. One third of the 416,000 projected deaths in the region over the next decade can be prevented with improvements in diagnosis and treatment. Accordingly, the WHO launched the Global Breast Cancer Initiative, calling on the international community to improve cancer care. Pathology capacity is essential to the accurate subtyping of breast cancers, directly linked to diagnosis and treatment. Here we report how we developed a program to train and engage pathology technicians in high-quality manual immunohistochemistry (IHC) in 10 sub-Saharan countries. 

Immunohistochemistry is a multistep process of tissue analysis. It involves stopping the degradation of tissue once removed from the patient, carefully processing tissue to expose antigens within cells, and staining the tissue with antibodies that specifically bind to antigens and enable the classification of tissues. IHC is used to determine the level of estrogen receptor, progesterone receptor, HER2/neu expression, and proliferation index in breast cancer—all critical information to guide treatment decisions. While the process is automated in many parts of the world, in low-resource settings (where equipment is expensive, often unavailable, and difficult to maintain) it is essential to develop a skilled workforce that can perform the detailed procedure manually with precision and in a timely manner to treat patients. While the idea of using “leapfrog” technologies such as RT-qPCR (real-time quantitative reverse transcription polymerase chain reaction) has been proposed for the classification of breast cancer phenotypes, a well-trained workforce in fundamental principles and methods is still needed.

We began with a project to build pathology capacity at Hawassa Specialized and Comprehensive Referral Hospital in Hawassa, Ethiopia. We recognized that sustained training, motivation, and involvement of laboratory technicians were crucial for the success of the program. We therefore partnered with a nonprofit organization with experience in virtual education technology platforms and an established network of relationships across sub-Saharan Africa. Through our surveys, pathology technicians across the region voiced their need for free access to high-quality, practical training focused on the technicians’ central responsibilities such as specimen handling and processing.

We mobilized a multidisciplinary international team to develop a long-term implementation project to address technicians’ needs through webinar-based lectures, continual digital mentorship, and the sharing of educational materials. Faculty included experienced laboratory technicians, pathologists, an immunologist, and a surgeon from the following nations: South Africa, Germany, Australia, USA, Kenya, and Ethiopia. Approximately 370 registrants from 11 sub-Saharan countries expressed their interest in the program launched in January 2022, with 266 participants from 10 countries attending live training sessions. Participants were from Burundi, Cameroon, Ethiopia, Gambia, Ghana, Kenya, Nigeria, Rwanda, Senegal, and Zambia. Laboratory technicians were our target audience, but pathologists and residents also registered. A total of 95 participants completed a pre-course survey. The majority of respondents (53.7%) reported that their institution did not perform IHC. Of those hospitals with IHC capacity, 89% performed it manually. We found that 74.2% of histotechnicians had more than five years of experience in their profession, although the majority (58.1%) had less than one year of experience performing IHC.

The three-day-long webinar consisted of six lectures in total. Topics included an overview of IHC theory, methods, and troubleshooting. Each lecture was followed by a question & answer (Q&A) session. The sessions lasted 1.5 hours and were scheduled in the morning so participants would still have a productive workday. The lecture slides, recordings, and written Q&A answers were provided. Since the webinar, recordings have been viewed 275 times. A post-course survey with 37 respondents found that 43% preferred using laptops and 41% mobile devices. The majority stated they felt comfortable using a social media platform for professional networking and sharing of educational materials—32% extremely comfortable and 49% very comfortable.

One of the most consistent themes throughout the webinar was the importance of optimizing pre-analytic variables related to breast cancer specimen handling. The surgical specimen should be handled with great care, as an extension of the patient, from the time it is excised in the operating room to the time of fixation in the pathology lab. The quality of immunohistochemical staining (and any other work using paraffin-embedded tissue) depends on this fundamental first step. We emphasized the importance of limiting cold ischemia time to less than one hour and fixing the specimen with adequate amounts of formalin in an appropriately sized container. The implementation of such best practices requires clear communication across multidisciplinary hospital teams, including surgeons, operating room nurses, laboratory technicians, and pathologists. Developing such quality improvement projects within hospitals can be implemented with minimal cost via sharing of previously established standard operating procedures (SOPs).

Recognizing that one-time educational interventions often do not result in a sustained impact, we then launched a digital mentorship platform. This venue allows lecturers and participants to engage in ongoing discussions, sharing of materials and SOPs, and the creation of lasting professional networks across hospitals and countries. Over 60 participants remain active through posts, comments, questions, and views of content. We invite participants to feature accomplishments, posts of quality improvement projects, and “how I do it” videos for participants to share.

In developing this implementation project, we designed a logic model to provide a useful framework. We aim to measure impact on individual participants; the community of African technicians; the programmatic changes within their institutions; and the implementation project as a whole. We are tracking program outcomes through pre- and post-course surveys, knowledge assessments, and observation of engagement on the digital mentorship platform. Our initial results demonstrated improvements in knowledge and confidence; however, further practical guidance and training is requested. Access to reagents has been discussed as a problem.

In order to improve breast cancer outcomes, we assembled a diverse international team focused on sustaining multidisciplinary collaboration and engagement in pathology education in sub-Saharan Africa. While we have started with immunohistochemical staining, future educational programs can also be developed. These efforts will contribute toward building the essential global workforce across disciplines that is needed to advance discoveries in breast cancer biology and novel treatments.

 References

1. McCormack V, McKenzie F, Foerster M, Zietsman A, Galukande M, Adisa C, Anele A, Parham G, Pinder LF, Cubasch H, Joffe M, Beaney T, Quaresma M, Togawa K, Abedi-Ardekani B, Anderson BO, Schüz J, Dos-Santos-Silva I. Breast cancer survival and survival gap apportionment in sub-Saharan Africa (ABC-DO): a prospective cohort study. Lancet Glob Health. 2020 Sep; 8(9):e1203–e1212. doi: 10.1016/S2214-109X(20)30261-8. PMID: 32827482; PMCID: PMC7450275.
2. Anderson BO, Ilbawi AM, Fidarova E, Weiderpass E, Stevens L, Abdel-Wahab M, Mikkelsen B. The Global Breast Cancer Initiative: a strategic collaboration to strengthen health care for non-communicable diseases. Lancet Oncol. 2021 May 1; 22(5): 578–81.
3. Martei YM, Pace LE, Brock JE, Shulman LN. Breast Cancer in Low- and Middle-Income Countries: Why We Need Pathology Capability to Solve This Challenge. Clinics in Laboratory Medicine. 2018 Mar 1; 38(1): 161–73.
4. Mugabe M, Ho KE, Ruhangaza D, Milner D, Rugwizangoga B, Chu VC, Wu NC, Rizo A, Weidler JM, Wong W, Bates M. Use of the Xpert Breast Cancer STRAT4 for Biomarker Evaluation in Tissue Processed in a Developing Country. American Journal of Clinical Pathology. 2021 Nov;156(5):766-76.

About Authors

Alemwosen Teklehaymanot Alem, M.D., Assistant Professor of Anatomic Pathology, Department of Pathology, College of Medicine and Health Sciences, Hawassa University, Ethiopia

As Head of the Pathology Department at Hawassa University, Dr. Alem oversees pathology services for patient referrals, teaches students, and advises postgraduate students on their research projects. Over the last two years, Dr. Alem has been leading a program training his staff to provide immunohistochemistry (IHC) services at Hawassa University Comprehensive Specialised Hospital. As of 2022, Dr. Alem’s team has commenced implementing IHC in the pathology lab and will be able to provide differentiated cancer diagnostic services for patients in southern Ethiopia and the Oromia region.

Katy M. Graef, Ph.D.; Vice President, Programs, BIO Ventures for Global Health, USA

Dr. Graef completed her Ph.D. in Virology at the University of Oxford, through the NIH Oxford-Cambridge Scholars Program. Her graduate studies examined host-pathogen interactions of influenza viruses. Following her graduate work, she became a postdoctoral research fellow at the Rocky Mountain Laboratories in Hamilton, Montana, where she studied tick-borne flaviviruses. At BIO Ventures for Global health, Dr. Graef leads the organization’s African Access Initiative (AAI), a public-private partnership focused on improving cancer patient outcomes in Africa.

Daniel Schmolze, M.D.; Assistant Clinical Professor, Department of Pathology, City of Hope National Medical Center, USA

Dr. Schmolze had a career as a software engineer before deciding to study medicine. He subsequently attended medical school at the University of Massachusetts in Worcester, Massachusetts, and went on to complete pathology residency at Beth Israel Deaconess Medical Center in Boston. He stayed on for a fellowship in breast pathology under the mentorship of Dr. Stuart Schmitt. Dr. Schmolze joined City of Hope in 2016. He currently leads the breast pathology group and also serves as the medical director of digital pathology, where he is overseeing the transition of the department of pathology to a digital workflow. Dr. Schmolze advises and engages in regular meetings with Dr. Alem to support capacity building at Hawassa University’s Department of Pathology.

Linda Setiawan, M.Sc.; Senior Program Manager, BIO Ventures for Global Health, USA

After completing her education at Free University Berlin, Linda Setiawan conducted academic research in the fields of molecular biology and genetics, resulting in several peer-reviewed publications. At BIO Ventures for Global Health, she leverages her research experience in the biological sciences to catalyze global research collaborations in the infectious disease space. Through the African Access Initiative, she develops and leads capacity-building projects that are driven by the needs of African cancer care providers.

Lesley Taylor, M.D.; Assistant Clinical Professor, Division of Breast Surgery, Department of Surgery, City of Hope National Cancer Center, USA.

Dr. Taylor has been involved with numerous initiatives in Ethiopia to strengthen breast cancer care, research, and education for over a decade. Dr. Taylor has had the privilege to contribute with international multidisciplinary teams on a variety of awards, including the Susan G. Komen Graduate Training Program in Disparities Research, which sponsored six Ethiopian graduate students pursuing breast cancer research. Dr. Taylor serves as a Technical Consultant for the WHO Global Breast Cancer Initiative. Dr. Taylor is actively involved with projects at the Hawassa University College of Medicine and Health Sciences within the oncology unit, school of nursing, and pathology department.