Breast Cancer In Low-resource Settings Research Articles

A multi-phase structured cascade model for mass training of community healthcare workers in performing clinical breast exams in remote regions.

Clinical breast exam (CBE) by outreach healthcare workers (HCW) may help downstage breast cancer in resource-limited areas where mammography may not be feasible. We evaluated the effectiveness of a pilot cascade-model training programme for HCWs in remote areas of Pakistan. The training programme comprised three phases. In phase one, fellowship-trained breast surgeons at a metropolitan academic centre trained six HCWs to perform CBEs. In phase two, these six HCWs (master trainers) trained 15 additional HCWs, implementing cascade training. In phase three, the consultant breast surgeon conducted a re-evaluation and refresher course for all 21 HCWs at least one year after the original training session. We assessed CBE ability and skills through pre- and post-changes through self-reported confidence and direct observation of procedural skills. Significant improvements in learners' self-reported confidence and CBE skills were observed in both phases one and two. The median scores in the learners' post-training self-reported confidence and CBE skills (inspection, palpation, and lymph node examination) improved by 20% and 46.2%, respectively, indicating excellent learning outcomes of the cascade training sessions. Phase three showed sustained high scores in self-reported confidence and CBE skills more than one year later. Mass training of outreach HCWs in remote regions in performing CBE may be possible with a structured multiphase cascade-training model and may be an important step in downstaging symptomatic breast cancer in low-resource settings.

Knowledge, practice and associated factors of breast self-examination among female university students of Bangladesh

BackgroundBreast cancer is the most common cancer and leading cause of death worldwide. Breast self-examination (BSE) is a cost-effective tool for self-assessment and for potential early detection of breast cancer in low-resource settings. This study aimed to explore knowledge, practice and associated factors of BSE among female university students of Bangladesh. MethodsA cross-sectional study was conducted among 400 conveniently selected female students aged ≥18 years from four universities. A pre-tested semi-structured self-administered questionnaire was used for data collection. Univariate and multivariable logistic regression and simple and multiple linear regression analysis was used to assess determinants of knowledge and practice regarding BSE. ResultsA total of 400 students participated from two private and two public universities (100 from each university). The average age of the participants was 20.89 ± 1.72 years (±SD). Of all, 60.5% had presence of knowledge (i.e., heard) about BSE. The average knowledge score was 7.41 ± 3.27 (in a scale of 0–15). Among those who had knowledge about BSE only 10.7% participants practiced it monthly. Being in public university (Adjusted Odds Ratio [aOR]: 3.42, 95% Confidence Interval [CI] 1.73–6.74) and years of education (aOR: 1.42, 95%CI: 1.02–1.97) were significant determinant of presence of knowledge regarding BSE. Moreover, studying in public university (β: 0.99, 95%CI 0.16–1.82) and education years passed (β: 0.51; 95%CI: 0.18–0.85) were associated with a higher knowledge score. Practice of BSE was negatively associated with students’ rural living prior to admission (aOR: 0.26, 95%CI: 0.08–0.79), and positively associated with level of knowledge regarding BSE (aOR: 1.48; 95%CI 0.08–0.79). ConclusionThis study revealed a general lack of knowledge and practice regarding BSE among female university students. As knowledge and practice of BSE would increase breast cancer awareness and screening acceptance, authorities should address the issue with properly planned strategies.

Abstract P1-01-06: Diagnostic accuracy of a novel palpation device to improve early detection of breast cancer in low-resource settings

Abstract Background and objectives: As the most commonly diagnosed cancer in women, breast cancer is projected to reach 1 million cases per year by 2020 in LMICs alone. Although incidence continues to increase in low- to middle-income countries, access to early detection in these high burden areas remain limited, in part due to lack of low-cost efficacious tools where mammography isn’t feasible. Therefore, the aim of this study is to evaluate the diagnostic accuracy of a lower cost, non-invasive, portable device called iBreastExam (iBE) in the detection of clinically relevant breast lesions. Methods: This study was a prospective non-randomized trial which enrolled women seeking routine screening or follow-up breast diagnostic evaluation from Nova Iguaçu and Rio de Janeiro, Brazil, respectively. Non-pregnant women aged 18 and older were eligible to enroll after providing informed consent. Each woman received an iBE palpation test and then mammography, ultrasound (US), or both, each by a different blinded clinician. For the sake of determining true lesion status, a positive mammogram was considered BIRADS 0, 3-6. A positive US was considered BIRADS 3-6. To assess accuracy of iBE to detect lesions, the sensitivity and specificity were calculated compared to mammography alone, ultrasound alone, or mammography plus ultrasound. For mammography plus US, the mammographic classification was considered the true status except for BIRADS 0, in which case the US classification was considered the truth. Each breast was considered an independent result for the sake of analysis. Results: The study enrolled and evaluated 226 women (449 breasts)with iBE, with a median age of 54 years old. Of the 434 breasts scanned by both iBE and mammography, 348 were normal by both and 17 lesions were detected by both. The sensitivity and specificity of iBE compared to mammography were 45.9% and 87.7%, respectively. Compared to the 324 US scans, where 258 normal by both and 20 lesions were detected by both, the sensitivity and specificity of iBE were 66.7% and 87.8%, respectively. Compared to mammography plus US, the sensitivity and specificity were 73.9% and 88.0%. Conclusions: Since iBE is being studied as a tool in resource-limited settings to facilitate early detection of suspicious breast lumps that warrant clinical follow-up, we chose other gold-standard diagnostic modalities and classifications, not detection of cancer, as our comparator. The relatively high specificity highlights the tools’ ability to reduce the pool of women warranting further evaluation but the sensitivity of iBE compared to mammography alone was relatively low. Notable, 15 of the 17 cases missed by iBE were classified as BIRADS 0. When these cases underwent US, the net sensitivity increased to 74%. These data highlight the potential for iBE to strengthen breast cancer early detection programs in LMIC’s and support the need for next generation sensors with improved sensitivity. Citation Format: Maurício M Costa, Anne F Rositch, Fernanda PA Pereira, Hildoberto C de Oliveira, Carolina F de Oliveira, Nilson Gomes, Flávia PPL Lopes. Diagnostic accuracy of a novel palpation device to improve early detection of breast cancer in low-resource settings [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-01-06.

Breast cancer subtypes: implications for the treatment and survival of patients in Africa—a prospective cohort study from Mozambique

BackgroundData regarding breast cancer epidemiology, treatment and survival in Africa are scarce. We aimed to assess the distribution of breast cancer subtypes in Mozambique and its impact on patients’ treatment and survival. The concordance of biomarker assessment between cytological and histological samples was also evaluated.MethodsProspective cohort study including 210 patients diagnosed between January 2015 and August 2017, followed to November 2019. Clinicopathological characteristics, treatment, 3-year overall survival (OS) and disease-free survival (DFS) were compared across classic tumour subtypes (oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, HER2-positive and triple-negative breast cancer (TNBC)) and surrogate intrinsic subtypes (St. Gallen classification). Concordance was measured using Cohen’s κ statistics.ResultsA total of 51% of patients had ER-positive/HER2-negative tumours, 24% HER2-positive and 25% TNBC. Concordance between cytological and histological samples regarding ER and HER2 status was substantial (κ=0.762 and κ=0.603, respectively). There were no significant differences across subtypes regarding clinical characteristics and treatment, except for HIV positivity and high histological grade (more prevalent among TNBC) or endocrine therapy (higher use among ER-positive/HER2-negative and HER2-positive patients). Three-year OS was 52.5% (95% CI, 44.3% to 60.0%), being higher in ER-positive/HER2-negative (61.1%) compared with HER2-positive (53.2%) and TNBC (31.9%) patients. Adjusted HRs were 1.96 (95% CI, 1.13 to 3.39) among HER2-positive and 3.10 (95% CI, 1.81 to 5.31) among TNBC versus ER-positive/HER2-negative patients. Three-year DFS was 46.6% (95% CI, 38.0% to 54.8%), being lower among TNBC versus ER-positive/HER2-negative patients (HR 2.91; 95% CI, 1.64 to 5.16). Results were similar between surrogate intrinsic subtypes.ConclusionThere was a high proportion of HER2-positive and TNBC among Mozambican patients and their survival was poor compared with ER-positive/HER2-negative patients, partly due to the limited treatment options. A systematic assessment of ER, PR and HER2 status is feasible and may help tailoring and optimise the treatment of patients with breast cancer in low-resource settings, potentially leading to survival gains in this underserved population.

Clinical Impact of Diagnostic Breast Ultrasound Performed by Generalist Doctors and Nurses in Rwanda

Purpose Diagnostic breast ultrasound (US) can be an important tool for the early detection of breast cancer in low-resource settings where efficient strategies to refine the likelihood of malignancy among palpable breast masses are needed. However, the feasibility and clinical role of breast US in such settings has not been described. We trained four general practitioners and five nurses in diagnostic breast US at a rural Rwandan district hospital that serves as a cancer referral facility. We examined management plans, biopsy rates, and patient diagnoses after trainee breast US to determine the impact on clinical care. Methods We abstracted US assessment forms and medical records to determine outcomes from trainee US during 21 months of in-person and electronic training by Boston-based radiologists. We examined management plans, biopsy rate, cancer detection rate, rate of benign diagnoses, and cancers diagnosed among patients discharged after initial evaluation. Results Between January 2016 and September 2017, 307 patients had trainee-performed diagnostic breast US. After US, 158 (51%) were recommended to undergo biopsy, 30 (10%) were recommended to have aspiration/drainage, 49 (16%) were recommended for clinical/US surveillance, one (0.3%) was referred elsewhere, 65 (21%) were discharged, and four—all with no abnormalities on US—had missing recommendations. Of those recommended for initial biopsy, 151 patients (96%) underwent biopsy at that time. Fifty-six patients (37%) were diagnosed with breast cancer, 44 (30%) with fibroadenoma, and 50 (33%) with other benign diagnoses. Among those with breast masses on US (n = 255), 149 patients (58%) underwent biopsy and 55 (22%) were diagnosed with cancer. As of November 2017, all patients ultimately diagnosed with cancer had had a biopsy at their initial visit. No patients who had been discharged or were receiving surveillance had been subsequently diagnosed with cancer. Conclusion Diagnostic breast US by general practitioners and nurses has been a useful tool for the evaluation of breast lesions at a rural Rwandan facility and has helped avoid biopsy for 42% of patients with breast masses on US. Clinical follow-up is ongoing to assess longer-term outcomes and examine cancer detection rates and loss-to-follow-up rates among patients not initially biopsied. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Lydia E. Pace Stock or Other Ownership: Firefly Health Sughra Raza Honoraria: Fujifilm Medical Services Travel, Accommodations, Expenses: Fujifilm Medical Services

Training to Improve the Quality of Early Detection of Breast Cancer in Low-Resource Settings

Purpose Breast cancer (BC) is the most common cancer among women in Latin America, yet many countries lack the capacity to provide early detection and diagnostic services. In Peru, mammograms are not readily available in secondary cities, and 57% of women who are diagnosed with BC are diagnosed with stage III and IV disease. To bring services to women in a northern region of Peru, PATH collaborated with Peruvian health institutions at the local, regional, and national levels to design and implement a strategic algorithm with which to increase the early detection of BC in the absence of mammography. Here, we evaluate the impact of training on the quality of clinical breast exam (CBE), ultrasound triage, and fine-needle aspiration (FNA) sampling and the reading of FNA biopsy for triage-positive women. Methods Two hundred twenty-four midwives and 15 doctors were included in two-step training in Trujillo, Peru. CBE trainings were performed using anatomic models and patient exams in 2-day sessions. Team discussion with trainers was used to improve skills. Doctors’ trainings for FNA sampling were led by two international expert pathologists in 2014 and by a Peruvian expert pathologist in 2016. Then in 2017, 43 pretraining and 50 post-training FNA biopsy samples were evaluated for adequacy and quality of diagnosis. Results Since the trainings, 14,223 women have received CBE on an opportunistic basis. Midwives refer abnormal cases (n = 281) for follow-up. All doctors felt well trained for CBE and FNA, whereas five of 15 doctors perceived the need for additional ultrasound training. Quality assessment revealed that the adequacy of FNA samples improved from 26% pretraining to 37% post-training. Of the 43 FNA samples, a low concordance with reviewers was observed in the detection of suspicious/carcinoma (6.9% v 13.9%), whereas full concordance was observed after the training, although the numbers were small. Conclusion In Peru, CBE remains an acceptable and feasible approach if complemented with ultrasound triage and FNA biopsy. Additional efforts are needed to increase coverage through a structured program. Training and continuous monitoring are essential for quality assurance. AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The following represents disclosure information provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more information about ASCO's conflict of interest policy, please refer to www.asco.org/rwc or ascopubs.org/jco/site/ifc . Ronald Balassanian Stock or Other Ownership: Cerus Corp ($400.00)

Early Clinical Impact of Diagnostic Breast Ultrasound Performed by General Practitioners and Nurses in Rwanda

Background: Diagnostic breast ultrasound (US) could be an important tool for early detection of breast cancer in low-resource settings, where efficient strategies to refine the likelihood of malignancy among palpable breast masses are needed. However, the feasibility and clinical role of diagnostic ultrasound in such settings has not been described. We trained 4 general practitioner doctors (GPs) and 5 nurses in diagnostic breast US at a rural district hospital in Rwanda that serves as a cancer referral facility. Aim: Assess management plans, biopsy rates and patient diagnoses after nurse- and GP-performed breast ultrasounds to determine the impact of diagnostic US on clinical care. Methods: We reviewed outcomes from trainees' ultrasounds during 21 months of in-person and electronic training and mentorship by Boston-based radiologists. Trainees' US assessments and management plans were recorded on structured clinical forms. Patient diagnoses and follow-up were extracted from medical records using a standardized data collection form. Among patients who received breast US, we examined a) clinicians' management plans; b) biopsy rate; c) cancer detection rate; c) rate of benign diagnoses; d) cancers diagnosed among patients who were sent home after initial evaluation. Results: Between January 1, 2016 and September 30, 2017, 307 patients with breast concerns had a diagnostic breast US and a documented trainee US assessment. Of these, following their initial US, 158 (51%) were recommended to receive a biopsy, 30 (10%) were recommended to have aspiration/drainage, 49 (16%) were recommended for clinical or US surveillance, 1 (0.3%) was referred to another facility, 65 (21%) were discharged, and 4 (all with no abnormalities on US) had missing recommendations. Of those recommended for biopsy at initial presentation, 151 (96%) had a biopsy at that time. 56 (37%) were diagnosed with breast cancer, 37 (25%) with fibroadenoma, 7 (5%) with lactating adenoma, and 50 (33%) with other benign diagnoses. Among those with breast masses on US (n=255), 149 (58%) received a biopsy and 55 (22%) were diagnosed with cancer. As of November 23, 2017, all patients ultimately diagnosed with cancer had had a biopsy at their initial visit, and no patients who had been discharged or recommended for clinical or radiographic surveillance had been subsequently diagnosed with cancer. Conclusion: Diagnostic breast US by GPs and nurses has been a useful tool in the evaluation of breast lesions, including palpable masses, at a rural cancer facility in Rwanda. Early findings suggest that it has allowed avoidance of biopsy for 42% of patients with breast masses noted on US. Clinical follow-up and evaluation are ongoing to assess longer-term patient outcomes, cancer detection rates among patients who are not initially biopsied, and rates of follow-up among patients recommended to have clinical or radiographic surveillance.

Abstract C48: Neoadjuvant endocrine therapy in locally advanced hormone receptor positive (HR+) breast cancer (BC) in a low-resource, middle-income setting (Guatemala)

Abstract Background: BC is the leading cause of cancer death in women in low- and middle-income countries (LMIC). For locally advanced BC, neoadjuvant treatment is often needed to downstage tumors prior to surgery, however many patients (pts) with BC in low-resource settings do not receive adequate therapy due to financial, social, and logistical barriers. This study evaluates the feasibility, adherence rates, and efficacy of neoadjuvant endocrine therapy with tamoxifen in a low-resource setting in Guatemala. Methods: This is a single arm, single center study of neoadjuvant tamoxifen in pts with locally advanced HR+ BC. Pts were treated with tamoxifen for 4-6 weeks then underwent a core biopsy of their primary tumor for Ki67 evaluation. If Ki67 was ≤ 10%, tamoxifen was continued for a total of 4 months. If Ki67 > 10%, pts were taken off study. The primary endpoint was assessing the proportion of pts who completed neoadjuvant treatment and received definitive surgery. Results: The median age was 59 years (range 35-78). Nine (25.7%) pts were pre-menopausal and 26 (74.3%) pts were post-menopausal. Ductal histology was present in 31 (88.6%) pts and lobular histology in 3 (8.6%) pts. Clinical stage was IIB in 5 (14.3%) pts, IIIA in 22 (62.9%) pts, IIIB in 7 (20%) pts, and IIIC in 1 (2.9%) pt. All pts were estrogen receptor positive (ER+), 29 (82.9%) pts were progesterone receptor positive (PR+), and 2 (5.7%) pts were HER2+. Of the 35 pts enrolled, 32 (91.4%) returned for a biopsy after 4 weeks of tamoxifen. Seventeen pts were taken off study; 8 pts had Ki67 > 10% and 9 pts had clinical progression. Fifteen (46.9%) pts continued on tamoxifen for 4 months. Of these, 13 pts (86.7%) underwent mastectomy. By exam, 6 pts had a complete response (CR) and 7 pts had a partial response. There was one pathologic CR. One pt was lost to follow-up and in one the tumor was still too large. The cost of neoadjuvant endocrine therapy with additional biopsy was 28% the cost of neoadjuvant chemotherapy in this setting. Conclusions: Neoadjuvant tamoxifen is a tolerable, acceptable, and less expensive option for pts with HR+ locally advanced BC in a middle-income, low-resource setting, with good rates of adherence and clinical response. This has implications for other LMIC, but further studies are needed to better define patient selection, applicability, and length of treatment of neoadjuvant tamoxifen Citation Format: Laila S. Agrawal, Mei-Ling Pereira, Ingrid A. Mayer, Eduardo Gharzouzi. Neoadjuvant endocrine therapy in locally advanced hormone receptor positive (HR+) breast cancer (BC) in a low-resource, middle-income setting (Guatemala). [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C48.

Recurrent BRCA1 and BRCA2 mutations in breast cancer patients of African ancestry

Recurrent mutations constituted nearly three quarters of all BRCA1 mutations and almost half of all BRCA2 mutations identified in the first cohort of the Nigerian Breast Cancer Study. To further characterize breast/ovarian cancer risks associated with BRCA1/BRCA2 mutations in the African diaspora, we genotyped recurrent mutations among Nigerian, African American, and Barbadian breast cancer patients. A replication cohort of 356 Nigerian breast cancer patients was genotyped for 12 recurrent BRCA1/2 mutant alleles (Y101X, 1742insG, 4241delTG, M1775R, 4359insC, C64Y, 1623delTTAAA, Q1090X, and 943ins10 from BRCA1, and 1538delAAGA, 2630del11, and 9045delGAAA from BRCA2) by means of SNaPshot followed by direct sequencing or by direct sequencing alone. In addition, 260 African Americans and 118 Barbadians were genotyped for six of the recurrent BRCA1 mutations by SNaPshot assay. Of all the BRCA1/2 recurrent mutations we identified in the first cohort, six were identified in 11 patients in the replication study. These mutation carriers constitute 3.1 % [95 % Confidence Interval (CI) 1.6-5.5 %] of the replication cohort. By comparison, 6.9 % (95 % CI 4.7-9.7 %) of the discovery cohort carried BRCA1/2 recurrent mutations. For the subset of recurrent mutations we tested in breast cancer cases from Barbados or the United States, only two 943ins10 carriers were identified in African Americans. Nigerian breast cancer patients from Ibadan carry a broad and unique spectrum of BRCA1/2 mutations. Our data suggest that BRCA1/2 mutation testing limited to recurrent mutations is not sufficient to understand the BRCA1/2-associated breast cancer risk in African populations in the diaspora. As the cost of Sanger sequencing is considerably reduced, deploying innovative technologies such as high throughput DNA sequencing of BRCA1/2 and other cancer susceptibility genes will be essential for identifying high-risk individuals and families to reduce the burden of aggressive early onset breast cancer in low-resource settings.

“We Are the World”…Applied to Cancer

As I thought about this issue and this editorial, and about the work we are doing together, the powerful song by multiple artists—including Michael Jackson, Lionel Richie, Tina Turner and a host of others—called “We Are the World” kept playing in my head. I’d suggest that each of you reading this go to the website [1], get yourself charged up by watching the video, and think about the solidarity that the “We Are the World” performance showcased, which was centered around the plight of Africa and the devastating consequences that famine was having there. Now let’s apply this solidarity to cancer as we work together to eradicate the ravages of this disease. Remember that this journal is “An Interdisciplinary Journal that Aims to Reduce the Burden of Cancer in the World Through Effective Education.” We have some heroes and extraordinary partners as we reach for these goals. The first person I want to pay tribute to is Darren Starmer, an extraordinary associate editor doing yeoman’s work to get articles from outside North America reviewed, critiqued and improved for this journal. If you look at any issue, there are articles from all over the world from good people doing good things, but in this issue alone, there are contributions from Crete, Italy, Nicaragua, China, Turkey, and Egypt. All of these provide cultural insights into the quest to eliminate disparities among our diverse populations in the US and Canada. A second editor who deserves special tribute is Amr Soliman, who along with his colleagues in Michigan, is helping to train a contingent of international cancer control experts. His work is detailed in an article in this issue. Amr introduced me to the exceptional work that Joe Hartford’s Office of International Affairs is doing at the NCI. I was deeply influenced by his recent paper, published in Lancet Oncology [2], that addresses strategies for dealing with breast cancer in low-resource settings. There is a fair amount of “pressure” on policy makers to institute organized breast cancer screening via mammography. Much less attention is being paid to the women with symptoms, including those that are diagnosed very late in the disease process. One point of the article is that it might be better to direct resources toward women who have breast cancer, rather than screening the whole population, the overwhelming majority of whom do not have breast cancer. One place where resources are scarce is in palliative care services. Joe’s wise message concerning this paper was: “I hope the paper will be of help to you since all of us are striving to do what we can with what we have.” Another voice of incredible wisdom from our editorial board is that of Frank Ferris, Director of International Programs, The Institute for Palliative Medicine at San Diego Hospice (check out their programs!) who is trying to bring palliative care to the world. Please have a look at a video Frank is involved with called “Cancer Pain” [3]. Here are some highlights from this latest “Treat the Pain/Life before Death” video: