Demonstration of an algorithm to overcome health system-related barriers to timely diagnosis of breast diseases in rural Zambia
Demonstration of an algorithm to overcome health system-related barriers to timely diagnosis of breast diseases in rural Zambia
Leeya F. Pinder 0 1
Jean-Baptiste Nzayisenga 0
Aaron Shibemba 0
Victor Kusweje 0
Hector Chiboola 0
Mary Amuyunzu-Nyamongo 0 3
Sharon Kapambwe 0
Catherine Mwaba 0 2
Pavlo Lermontov 0
Chibamba Mumba 0
Ronda Henry-Tillman 0
Groesbeck P. Parham 0 1
Saharan Africa. 0
0 Editor: Peter C. Angeletti, University of Nebraska- Lincoln , UNITED STATES
1 Department of Obstetrics and Gynecology, Division of Global Women's Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States of America, 2 Department of Obstetrics and Gynecology, Women and Newborn Hospital , Lusaka Zambia, Lusaka , Zambia , 3 Department of Pathology, Kabwe General Hospital , Kabwe , Zambia , 4 Department of Social Sciences, Chreso University , Lusaka , Zambia
2 Cancer Diseases Hospital , Lusaka , Zambia , 8 Department of Surgery, University of Arkansas for Medical Sciences , Little Rock, AR , United States of America
3 African Institute for Health and Development, Nairobi, Kenya, 6 Ministry of Health , Lusaka , Zambia
Eleven hundred and twenty-nine (1129) women attended the camps for breast care. Mean
age was 35.9 years. The majority were multiparous (79.4%), breast-fed (76.0%), and
reported hormone use (50.4%). Abnormalities were detected on clinical breast examination
in 122 (10.8%) women, 114 of whom required ultrasound. Of the 114 who underwent
Funding: This work was supported by the Susan G.
Komen Breast Cancer Foundation, GSP15UNC002
(GP). The funders had no role in study design, data
collection and analysis, decision to publish, or
preparation of the manuscript.
Competing interests: The authors have declared
that no competing interests exist.
ultrasound, 48 had identifiable lesions and were evaluated with ultrasound-guided core
needle biopsy (39) or fine-needle aspiration (
). The concordance between imprint cytology and
histopathology was 100%, when breast specimens were classified as either benign or
malignant. However, when specimens were classified by histopathologic subtype, the
concordance between imprint cytology and histology was 85.7% for benign and 100% for
malignant lesions. Six (
) women were diagnosed with invasive cancer. Eighteen (
women with symptomatic breast lesions had next-day surgery.
Similar to its impact on cervical cancer prevention services, a single visit breast care
algorithm has the potential to overcome health system-related barriers to timely diagnosis of
breast diseases, including cancer, in rural African settings.
Globally, the incidence of breast cancer is projected to surge over the next two decades, largely
due to increases in ageing populations, reductions in mortality from infectious diseases and
shifts in lifestyle risk factors, such as reproductive patterns, tobacco use and obesity [1±4].
Approximately 70% of new cases will occur in low- and middle-income countries (LMICs) 
where health systems are commonly characterized by underfunding and scarce mid- and
highlevel human resources. Women living in sub-Saharan Africa (SSA) will be profoundly affected,
as most typically present with late stage disease, resulting in 5-year relative survival rates
of < 50% (2±4). Those residing in rural Africa have an even higher percentage of late stage
disease than their urban counterparts [5±7]. Zambia, a country already heavily burdened with
HIV and cervical cancer [8±10], is predicted to have a 25% increase in incident breast cancer
cases and deaths by the year 2020 .
Having made cancer control a national priority, the Zambian Ministry of Health avidly
supports and facilitates the implementation of contextually appropriate and sustainable approaches
to early detection and treatment . In 2005, the burden of cervical cancer among previously
unscreened women in Zambia was addressed through the establishment of a public-sector
ªscreen and treatº prevention program  that links screening, using visual inspection with
acetic acid (VIA), to immediate treatment of precancerous lesions with either cryosurgery,
thermocoagulation or electrosurgical excision. Intervening histologic evaluation is reserved for cases of
suspected cancer. This WHO-approved single-visit approach to cervical cancer prevention in
resource-constrained environments avoids delays in diagnosis and treatment, and significantly
reduces loss to follow-up, in contrast to the prolonged, multi-step Pap
smear/HPV-colposcopybiopsy-histologic assessment-treatment algorithm commonly used in high-income settings.
To date, over 500,000 women have been screened throughout Zambia using this method.
Central to its success are the immediacy of test results and compression of the prevention
pathway into a single visit. Using lessons learned from the cervical cancer prevention experience,
we sought to improve time to diagnosis through the design and implementation of a
singlevisit algorithm for breast care.
The breast care clinical pathway is a multi-step process that involves awareness±screening±
radiographic imaging±cytohistologic examination±treatment. Long delays before, at or
2 / 11
between each step can significantly contribute to advanced presentations of both benign and
malignant diseases . We designed an algorithm that compresses the multi-step pathway
into a single visit, during which the following services are made available: (
) lay psychosocial counseling, (
) clinical breast examination (CBE), (
) ultrasound-guided breast biopsy, as indicated, (
) imprint cytology of breast biopsy
) post-cytology counseling, and (
) immediate surgical treatment or referral. The
algorithm was implemented within the context of two separate, week-long, breast care
outreach camps inside government-operated health facilities located in a predominantly rural
The preparatory phase of the project involved assembling local healthcare experts from
multiple disciplines±health promotion, lay counseling, nursing, radiology, pathology, general
surgery±as well as stakeholders from civil society (religious leaders, women's health advocates,
traditional healers, etc.), over a two-week period, to develop a breast care manual. The manual
was designed to equip the user with relevant competencies in breast care, inclusive of breast
cancer control. Once completed, the manual was used by the cadre of local experts (Master
Trainers) to train others (Training of Trainers), who in turn trained local healthcare providers
who were located at the proposed rural outreach sites. The trainees that were trained by the
Master Trainers consisted of four peer educators (health promotion), two lay counselors (lay
psychosocial counseling), four nurses (clinical breast examination), two radiographers (breast
ultrasound), two general medical officers (ultrasound-guided biopsy of the breast) and two
cytohistology technicians (imprint cytology). Two local general surgeons had previously been
trained in modern methods of surgical management of breast abnormalities under another
Susan G. Komen-sponsored program .
One week prior to the outreach camps, peer educators travelled throughout the catchment
areas (Kapiri Mposhi District±pop. 303,263; Kabwe DistrictÐpop. 202,914) in the Central
Province, raising awareness through messaging that (a) stressed the importance of breast
health, (b) listed the common signs and symptoms of breast cancer, and (c) provided the dates
and location of the event. Information leaflets were handed out and public announcements
were made using a mobile PA system targeting strategic sites such as local markets and
residential areas. Radio interviews with peer educators were conducted, coupled with continuous
radio announcements detailing the upcoming event. All messaging was conducted in English
and local languages.
Single visit breast care outreach camp
The breast care camps were conducted at government-operated heath facilities, one a primary
health clinic (Kapiri Mposhi Urban Clinic), and the other a provincial district hospital (Kabwe
General Hospital). During the camps, all service components in the breast care pathway were
bundled into a single visit format, including an option for surgery, if indicated. (Fig 1). Each
service was offered in separate, but adjoining rooms, in the following manner: Step
1ÐPreCounseling±conducted by lay counselors to explain to women the intent and value of the
various services that were being offered; to emphasize the importance of knowing what is normal
for their breasts as a component of breast self-awareness; and to address any questions, fears,
myths and misunderstandings women might have. Step 2ÐClinical Breast
Examination±conducted by nurses who provided instructions on how to perform self-breast examination, as
part of breast self-awareness, and information on the common signs and symptoms of breast
cancer. Women found to have breast abnormalities were immediately navigated to the Breast
3 / 11
Fig 1. Breast care model flow diagram.
Ultrasound Room for evaluation. Step 3ÐBreast Ultrasound and Ultrasound-guided Core
Biopsy/Needle Aspiration±performed by radiographers and general medical officers/general
surgeons, respectively, following written informed consent by the woman. Step 4ÐImprint
Cytology±conducted by cytohistology technicians who obtained cytology specimens from the
fresh breast core biopsies or aspirates and made cytology slides (imprint cytology) onsite,
which were immediately interpreted by the camp pathologist. Cytology results were given to
the participant by the general medical officer/general surgeon, with the understanding that it
was a provisional diagnosis. Each afternoon, specimens previously fixed in formalin were
delivered to the nearest pathology lab (Kabwe General Hospital) where they were rapidly
processed for final histologic diagnosis. One day later, histologic analyses were made available and
final results given to women by the physician who performed the biopsy. Step 5ÐLay
Counseling±provided again, but this time to women diagnosed with breast abnormalities that either
required some form of treatment, or observation. The primary purpose was to stress the
importance of follow-up at Kabwe General Hospital and to assist in the organization of
transportation. Step 6ÐBreast Surgery±offered to those in whom abnormal histopathology was
confirmed, surgical resection was indicated, and could be safely and effectively accomplished
at the local medical facility. Written consent was obtained prior to the surgical procedure
4 / 11
Eleven hundred and twenty-nine (1129) women attended the two camps and all received
breast health counseling and clinical breast examination. Mean age of camp participants was
35.9 years (±13.0). HIV positivity was 19% (228). The majority (79.4%) had at least one
pregnancy and breastfed (76.0%), while half (50.4%) reported hormone use, the majority of which
were estrogen-containing products (71.6%) (Table 1). Breast abnormalities were clinically
detected in 122 (10.8%) women (Table 2) of which 114 were referred for evaluation with
ultrasound. Of the 114 evaluated with ultrasound, 53 (46.5%) had normal findings and were
counselled to repeat CBE in 1 year or earlier if symptomatic. Fifty-nine (51.8%) women underwent
either ultrasound-guided core needle biopsy for solid-appearing lesions (39), fine-needle
aspiration for cystic-appearing lesions (
), local excision for lesions not amenable to needle biopsy
), or cyst drainage (
) (Table 2). One woman had two separate lesions that required biopsy
and cyst drainage. Another, age 15 years, was not desirous of further diagnostic evaluation of a
palpable breast mass. Data are missing on one participant. All specimens obtained through
biopsy or aspiration were immediately processed, on-site, for imprint cytology and confirmed
histologically in the referral pathology lab. Concordance between cytology and histology was
100% when classifying breast lesions as benign or malignant. Concordance between cytology
and histology was 85.7% for benign lesions and 100% for malignant lesions, when classifying
One womanÐrepeat clinical breast exam in 3 months
§ Five womenÐreferred to gynecologist for further management; one to return for CBE in 3 months; one received topical treatment for breast skin disorder
² Four women with multiple breast lesionsÐtriaged to observation
them according to histopathologic subtype. Fibroadenoma (
) was the most common benign
diagnosis (Table 3). Twenty-two (
) women underwent surgical excision for treatment or
diagnosis of symptomatic breast lesions. Less than 1% (6/1129) were diagnosed with invasive
cancer, all of whom had follow-up care immediately arranged at the nearby provincial hospital
(Kabwe General Hospital).
During the course of the single-visit breast care camps, trainers from Lusaka provided the
following clinical educational services for local healthcare providers at the rural outreach sites:
two cervical cancer prevention nurses were taught how to perform CBE, the breast ultrasound
skills and techniques of four radiographers were updated, three general medical officers were
mentored in ultrasound-guided core needle biopsy, two cytohistology technicians were trained
to perform imprint cytology, and two local lay persons were instructed in lay counseling.
In general, delays from symptom onset to time of diagnosis can potentiate advanced
presentations of breast diseases. Where breast cancer is concerned, the evidence is substantial that
delays of more than 3 months from symptom recognition to diagnosis is associated with late
stage presentation and poorer survival . In sub-Saharan Africa, where breast cancer is
commonly characterized by advanced stage (45±90% stage III and IV) at the time of diagnosis
[5, 7, 16, 17], and low ( 50%) 5-year survival rates [13, 17, 18], these delays average 6 months
or greater . Delays can be further stratified into woman-level (e.g. low educational level,
poor socioeconomic status, living in a rural area, poor breast cancer awareness, belief in
traditional or spiritual medicine) and health system-related (e.g. distance to nearest healthcare
provider, number of healthcare providers visited prior to diagnosis, health professionals with poor
breast cancer knowledge, unavailability of suitable diagnostic facilities, lack of appropriate
referral pathways) [5, 7, 20].
We implemented a breast care algorithm with the aim of overcoming health system-related
barriers to timely diagnosis of breast diseases. Breast health education, clinical breast
examination, radiographic imaging, cytohistologic diagnosis and immediate treatment or referral
services were offered in a single-visit format. Over 1,000 women attended the two, week-long,
breast care outreach camps. While the vast majority (88.9%) did not have a clinically detectable
lesion, they all received breast health promotion messages and were taught the importance of
breast self-awareness and CBE. For those with clinically detectable lesions, the outreach camps
provided same-day evaluation of the abnormalities, effectively eliminating multiple visits to
different tiers of the healthcare system and the associated costs and time of doing so, all of
which are associated with loss to follow-up [2, 7, 21±23]. The option of immediate surgical
intervention following histologic confirmation was accepted by 24 of the 25 (96%) women to
whom it was offered. In addition, those with breast cancer received an immediate referral for
To our knowledge this is the first breast care model of its type to be implemented in
subSaharan Africa, inclusive of an option for next-day surgical intervention.
There are several areas in which improvements can be made:
) The overall turnout at each event exceeded our expectations (avg. >110
women/day; peak 171). We made adjustments by increasing the numbers of CBE nurses,
radiographers, ultrasound machines and surgeons. Task-shifting administrative responsibilities
(patient registration, data collection, etc.) to non-clinical personnel would allow healthcare
providers the opportunity to focus solely on clinical issues. (
) Some women requested cervical
cancer screening in addition to breast care services. Modifying the service platform to include
cervical cancer screening would provide access to preventative, diagnostic and treatment
services for the two most common cancers affecting women in Zambia and sub-Saharan Africa.
Packaging or bundling multiple services as we did requires the coordinated efforts and
physical presence of many specialists in one place, and at the same time. The scarcity of
midand high-level human resources in resource-constrained settings represents a potential
limitation to bringing such a model to scale. However, human resource gaps can be filled using
modern telecommunications technology, e.g., cytotechnologists at the point-of-care can be taught
to prepare imprint cytology samples, identify and take digital images of the worst appearing
7 / 11
areas on the glass slide, and electronically submit them to an offsite pathologist;
ultrasonographers and nurses can be trained to perform ultrasound-guided biopsies, while being
monitored using teleproctoring technology. Drones can be used to transport biopsy/cytology
specimens to nearby pathology labs for final diagnosis.
Targeted Population: (
) The mean age of women attending the first outreach was 34.5
years (Table 1), whereas the majority of women in sub-Saharan Africa diagnosed with breast
cancer are between ages 35±49 years. During the second outreach camp, we modified health
promotion activities to target locations that would potentially increase access to older women,
such as local churches. This resulted in an increase in the mean age of women in the second
camp from 34.5 to 37.3 years (Table 1). (
) The breast cancer detection yield was relatively low.
Of the women with ultrasound-confirmed breast masses (Kapiri± 11.8%; Kabwe± 12.5%), only
12.2% had histologically-confirmed invasive breast cancers. In studies of SSA women
presenting to clinical care facilities with palpable breast masses, 16±34% were diagnosed with invasive
breast cancer [24±27]. (
) Although most breast masses detected in women are not cancerous,
they can seriously impact quality of life, and thus demand the serious attention of healthcare
providers [28, 29]. Of the 48 women evaluated with core biopsy or needle aspiration, 87.5%
had benign disease. There is a paucity of information regarding the prevalence of benign breast
diseases in women who reside in resource-constrained settings [27, 30, 31]. In a recent
retrospective study of a random sample of 365 women presenting to a walk-in breast specialist
center in South Africa, over 50% were diagnosed with benign disease compared to 14% with
breast cancer .
Targeted educational programs designed to increase breast cancer awareness and dispel
myths and misconceptions, may increase the breast cancer detection yield of outreach efforts.
Implementation of these programs in areas frequented by older women, such as local churches
and markets, may increase the likelihood of their participation. Further facilitation of access
through home-based clinical breast examinations with subsequent transport to clinical
facilities (e.g. breast outreach camps) of those with detected abnormalities, may also increase the
breast cancer yield. Lastly, partnering with local leaders and civic organizations to more deeply
engage the community, in addition to mass media campaigns, could impact outcomes.
A clinical service platform that provides comprehensive breast care to the highest-risk
individuals, differentiates between benign and malignant disease, and does so in a single-visit
setting, may effectively reduce bottlenecks within an already strained healthcare system, and limit
costly delays in care.
In order to determine the impact of a single-visit breast care algorithm and further define the
magnitude of breast disease in Zambia, we strongly recommend the implementation of this
approach on a larger scale, in both urban and rural settings. As with the cervical cancer
prevention program scale-up , partnerships with the Ministry of Health and local and
international stakeholders, in addition to leveraging and strengthening existing healthcare
infrastructure while building upon the network of previously trained healthcare providers, will
prove critical to its success. Continued use of the philosophy of adaptive innovation which, in
principle, incorporates respect for local beliefs and culture while integrating new ideas and
technology that fit the local circumstances, is mandatory.
Programmatic components should include (
) quality-assurance and quality control
measures at all levels, (
) impact evaluation, (
) cost and cost-effectiveness evaluations (
time-flow analysis (
) improved laboratory capacity, particularly the ability to perform
immunohistochemistry and identification of significant tumor biomarkers and (
8 / 11
of strategies to decrease loss to follow-up among women receiving care, particularly those
diagnosed with cancerous lesions.
Over the next two decades breast cancer incidence and mortality will double across the globe.
The impact on women residing in sub-Saharan Africa will be profound if effective and
affordable approaches to early detection and treatment are not rapidly employed and brought to
scale. The overall outcome of our single-visit model encourages its replication and scale-up to
improve the quality of breast care in such settings.
The success of this work is due in part to the commitment of the Project Coordinators Mildred
Lusaka and Tamala Goma, the staff of CBE nurses, radiographers, cytohistotechnicians and lay
Conceptualization: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor
Kusweje, Hector Chiboola, Mary Amuyunzu-Nyamongo, Ronda Henry-Tillman, Groesbeck P.
Data curation: Leeya F. Pinder, Aaron Shibemba.
Formal analysis: Leeya F. Pinder.
Funding acquisition: Groesbeck P. Parham.
Investigation: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor Kusweje,
Pavlo Lermontov, Chibamba Mumba, Ronda Henry-Tillman, Groesbeck P. Parham.
Methodology: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor Kusweje,
Hector Chiboola, Mary Amuyunzu-Nyamongo, Ronda Henry-Tillman, Groesbeck P.
Project administration: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor
Kusweje, Pavlo Lermontov, Chibamba Mumba, Groesbeck P. Parham.
Resources: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor Kusweje,
Sharon Kapambwe, Catherine Mwaba, Pavlo Lermontov, Chibamba Mumba, Groesbeck P.
Supervision: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor Kusweje,
Sharon Kapambwe, Catherine Mwaba, Groesbeck P. Parham.
Validation: Leeya F. Pinder, Aaron Shibemba, Groesbeck P. Parham.
Visualization: Leeya F. Pinder.
Writing ± original draft: Leeya F. Pinder, Jean-Baptiste Nzayisenga, Aaron Shibemba, Victor
Kusweje, Hector Chiboola, Mary Amuyunzu-Nyamongo, Sharon Kapambwe, Catherine
Mwaba, Pavlo Lermontov, Chibamba Mumba, Ronda Henry-Tillman, Groesbeck P.
Writing ± review & editing: Leeya F. Pinder, Groesbeck P. Parham.
9 / 11
10 / 11
1. Anderson BO , Ilbawi AM , El Saghir NS . Breast cancer in low and middle income countries (LMICs): a shifting tide in global health . Breast J . 2015 ; 21 ( 1 ): 111 ±8. https://doi.org/10.1111/tbj.12357 PMID: 25444441 .
2. Corbex M , Burton R , Sancho-Garnier H . Breast cancer early detection methods for low and middle income countries, a review of the evidence . Breast . 2012 ; 21 ( 4 ): 428 ± 34 . https://doi.org/10.1016/j. breast. 2012 . 01 .002 PMID: 22289154 .
3. Pace LE , Shulman LN . Breast Cancer in Sub-Saharan Africa: Challenges and Opportunities to Reduce Mortality . Oncologist . 2016 ; 21 ( 6 ): 739 ± 44 . Epub 2016/04/20. https://doi.org/10.1634/theoncologist. 2015-0429 PMID: 27091419; PubMed Central PMCID : PMCPMC4912363 .
4. El Saghir NS , Adebamowo CA , Anderson BO , Carlson RW , Bird PA , Corbex M , et al. Breast cancer management in low resource countries (LRCs): consensus statement from the Breast Health Global Initiative . Breast . 2011 ; 20 Suppl 2 : S3 ± 11 . https://doi.org/10.1016/j.breast. 2011 . 02 .006 PMID: 21392996 .
5. Jedy-Agba E , McCormack V , Adebamowo C , Dos-Santos-Silva I . Stage at diagnosis of breast cancer in sub-Saharan Africa: a systematic review and meta-analysis . Lancet Glob Health . 2016 ; 4 ( 12 ):e923± e35 . https://doi.org/10.1016/ S2214 -109X( 16 ) 30259 - 5 PMID: 27855871 .
6. Kantelhardt EJ , Frie KG . How advanced is breast cancer in Africa? Lancet Glob Health . 2016 ; 4 ( 12 ): e875± e6 . https://doi.org/10.1016/ S2214 -109X( 16 ) 30283 - 2 PMID: 27855857 .
7. Akuoko CP , Armah E , Sarpong T , Quansah DY , Amankwaa I , Boateng D . Barriers to early presentation and diagnosis of breast cancer among African women living in sub-Saharan Africa . PLoS One . 2017 ; 12 ( 2 ):e0171024. https://doi.org/10.1371/journal.pone.0171024 PMID: 28192444 .
8. Central Statistics Office Zambia. Zambia Demographic and Health Survey 2013 ± 14 . Rockville , Maryland, USA: 2014 .
9. International Agency for Research on Cancer. GLOBOCAN 2012 : Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2012 . 2012 .
10. Bateman AC , Katundu K , Mwanahamuntu MH , Kapambwe S , Sahasrabuddhe VV , Hicks ML , et al. The burden of cervical pre-cancer and cancer in HIV positive women in Zambia: a modeling study . BMC CANCER . 2015 ; 15 ( 1 ): 541 . https://doi.org/10.1186/s12885-015 -1558-5 PMID: 26205980
11. Ferlay J , Shin HR , Bray F , Forman D , Mathers C , Parkin DM . Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008 . Int J Cancer . 2010 ; 127 ( 12 ): 2893 ± 917 . https://doi.org/10.1002/ijc.25516 PMID: 21351269 .
12. Parham GP , Mwanahamuntu MH , Kapambwe S , Muwonge R , Bateman AC , Blevins M , et al. Population-level scale-up of cervical cancer prevention services in a low-resource setting: development, implementation, and evaluation of the cervical cancer prevention program in Zambia . PLoS One . 2015 ; 10 ( 4 ):e0122169. https://doi.org/10.1371/journal.pone.0122169 PMID: 25885821; PubMed Central PMCID : PMCPMC4401717 .
13. McKenzie F , Zietsman A , Galukande M , Anele A , Adisa C , Cubasch H , et al. African Breast Cancer-Disparities in Outcomes (ABC-DO): protocol of a multicountry mobile health prospective study of breast cancer survival in sub-Saharan Africa . BMJ Open . 2016 ; 6 ( 8 ):e011390. https://doi.org/10.1136/ bmjopen-2016-011390 PMID: 27554102; PubMed Central PMCID : PMCPMC5013398 .
14. Pinder LF , Henry-Tillman R , Linyama D , Kusweje V , Nzayisenga J-B, Shibemba A , et al. Leveraging an existing cervical cancer prevention service platform to initiate breast cancer control services in Zambia± Experiences and early outcomes . [Manuscript]. In press 2017 .
15. Richards MA , Westcombe AM , Love SB , Littlejohns P , Ramirez AJ . Influence of delay on survival in patients with breast cancer: a systematic review . Lancet . 1999 ; 353 ( 9159 ): 1119 ± 26 . Epub 1999/04/21. PMID: 10209974 .
16. Ginsburg O , Bray F , Coleman MP , Vanderpuye V , Eniu A , Kotha SR , et al. The global burden of women's cancers: a grand challenge in global health . Lancet . 2016 . https://doi.org/10.1016/S0140- 6736 ( 16 ) 31392 - 7 PMID: 27814965 .
17. Sankaranarayanan R , Swaminathan R , Brenner H , Chen K , Chia KS , Chen JG , et al. Cancer survival in Africa, Asia, and Central America: a population-based study . Lancet Oncol . 2010 ; 11 ( 2 ): 165 ± 73 . https://doi.org/10.1016/S1470-2045( 09 ) 70335 - 3 PMID: 20005175 .
18. Vanderpuye V , Grover S , Hammad N , PoojaPrabhakar, Simonds H , Olopade F , et al. An update on the management of breast cancer in Africa . Infect Agent Cancer . 2017 ; 12 : 13 . Epub 2017/02/24. https://doi. org/10.1186/s13027-017-0124-y PMID: 28228841 ; PubMed Central PMCID : PMCPMC5307840 .
19. Ezeome ER . Delays in presentation and treatment of breast cancer in Enugu, Nigeria . Niger J Clin Pract . 2010 ; 13 ( 3 ): 311 ± 6 . Epub 2010/09/23. PMID: 20857792 .
20. Brinton LA , Figueroa JD , Awuah B , Yarney J , Wiafe S , Wood SN , et al. Breast cancer in Sub-Saharan Africa: opportunities for prevention . Breast Cancer Res Treat . 2014 ; 144 ( 3 ): 467 ± 78 . https://doi.org/10. 1007/s10549-014-2868-z PubMed Central PMCID: PMCPMC4023680. PMID: 24604092
21. Kohler RE , Gopal S , Miller AR , Lee CN , Reeve BB , Weiner BJ , et al. A framework for improving early detection of breast cancer in sub-Saharan Africa: A qualitative study of help-seeking behaviors among Malawian women . Patient Educ Couns . 2017 ; 100 ( 1 ): 167 ± 73 . https://doi.org/10.1016/j.pec. 2016 . 08 . 012 PMID: 27528411; PubMed Central PMCID : PMCPMC5301948 .
22. Denny L , Sanjose Sd , Mutebi M , Anderson BO , Kim J , Jeronimo J , et al. Interventions to close the divide for women with breast and cervical cancer between low-income and middle-income countries and highincome countries . The Lancet [Internet] . 2016 November 3 , 2016 . Available from: http://www.thelancet. com/journals/lancet/article/PIIS0140- 6736 ( 16 ) 31795 - 0 /fulltext.
23. Anderson BO . Breast cancer in Sub-Saharan Africa: where can we go from here? J Surg Oncol . 2014 ; 110 ( 8 ): 901 ±2. https://doi.org/10.1002/jso.23825 PMID: 25351870 .
24. Jeje EA , Mofikoya BO , Oku YE . Pattern of breast masses in Lagos: a private health facility review of 189 consecutive patients . Nig Q J Hosp Med . 2010 ; 20 ( 1 ): 38 ± 41 . PMID: 20450030 .
25. Njeze GE . Breast lumps: a 21-year single-center clinical and histological analysis . Niger J Surg . 2014 ; 20 ( 1 ): 38 ± 41 . https://doi.org/10.4103/ 1117 - 6806 .127111 PMID: 24665202; PubMed Central PMCID : PMCPMC3953633 .
26. Ahmed HG , Ali AS , Almobarak AO . Frequency of breast cancer among Sudanese patients with breast palpable lumps . Indian J Cancer . 2010 ; 47 ( 1 ): 23 ±6. https://doi.org/10.4103/ 0019 - 509X .58854 PMID: 20071785 .
27. Ohene-Yeboah M , Amaning E. Spectrum of complaints presented at a specialist breast clinic in kumasi, ghana . Ghana Med J. 2008 ; 42 ( 3 ): 110 ± 3 . PMID: 19274109; PubMed Central PMCID : PMCPMC2643436 .
28. Maguire P. ABC of breast diseases . Psychological aspects. BMJ . 1994 ; 309 ( 6969 ): 1649 ± 52 . PMID: 7819954; PubMed Central PMCID : PMCPMC2542001 .
29. Stotland NL , Stewart DE . Psychological aspects of women's health care: the interface between psychiatry and obstetrics and gynecology . 2nd ed. Washington, D.C.: American Psychiatric Press; 2001 . xviii, 654 p. p.
30. Okoth C , Galukande M , Jombwe J , Wamala D. Benign proliferative breast diseases among female patients at a sub-Saharan Africa tertiary hospital: a cross sectional study . BMC Surg . 2013 ; 13 :9. https://doi.org/10.1186/ 1471 -2482-13-9 PMID: 23548039; PubMed Central PMCID : PMCPMC3623623 .
31. Pace LE , Dusengimana JM , Hategekimana V , Habineza H , Bigirimana JB , Tapela N , et al. Benign and Malignant Breast Disease at Rwanda's First Public Cancer Referral Center . Oncologist. 2016 ; 21 ( 5 ): 571 ±5. https://doi.org/10.1634/theoncologist.2015-0388 PMID: 27009935; PubMed Central PMCID : PMCPMC4861361 .
32. Rayne S , Lince-Deroche N , Hendrickson C , Shearer K , Moyo F , Michelow P , et al. Characterizing breast conditions at an open-access breast clinic in South Africa: a model that is more than cancer care for a resource-limited setting . BMC Health Serv Res . 2017 ; 17 ( 1 ): 63 . https://doi.org/10.1186/s12913- 016-1959-4 PMID: 28109290; PubMed Central PMCID : PMCPMC5251303 .