Appendix C.

Factors associated with delayed presentation and delayed diagnosis or start of treatment of breast cancer in Africa: summary of the findings reported by the studies included in the review

Author, year [ref no] (country)	Factors associated with delay between symptoms recognition and first visit to an HCP		Factors associated with delay between first visit to an HCP and BC diagnosis or start of treatment
	Crude	Adjusted	Crude	Adjusted
North Africa
Ahmed, 2014 [11]† (Sudan)	Factors associated with late presentation in patients with locally advanced breast cancer (%) Lack of education: 39.5% Financial aspects: 28.6% Use of traditional medicine: 13.8% Limited access to medical care: 9% Ignorance: 6.9% Fear of being a burden to relatives: 2.7%		n/a
Aloulou, 2015 [12] (Morocco)	Reasons for delays from symptoms recognition to diagnosis: Fear of cancer and/or treatment: 4%; Financial problems: 40%; Tried traditional treatments: 20% Health services: Distance from health center: 23%; Wrong diagnosis: 6%; Inadequate medical care: 7%
Benbakhta, 2015 [13] (Morocco)	Delay from symptoms recognition to presentation >2.2 mo: OR (95% CI) Socioeconomic: Aged >65 versus <45 y: 1.68 (0.64, 4.38) Rural versus urban area of residence: 4.62 (2.24, 9.52) Illiteracy versus secondary/university: 4.56 (2.26, 9.18) Employed versus housewife: 0.23 (0.13, 0.57) Low versus mid socioeconomic level: 8.55 (3.16, 23.17) >5 people in household: 2.05 (1.14, 3.69) BC awareness: No knowledge versus knowledge of BSE: 17.88 (8.74, 36.56) Positive versus negative family history: 2.51 (1.23, 5.13) Type of symptoms: Presence of typical versus atypical symptoms: 0.75 (0.33, 1.67) Health services related: Distance from HCP of presentation ≥100 versus <100 km: 8.62 (1.01, 67.14)	Delay from symptoms recognition to presentation >2.2 mo: OR* (95% CI) Socioeconomic: Rural versus urban area of residence: 3.00 (1.24, 7.23) Illiteracy versus secondary/university: 4.90 (2.50, 6.30) Employed versus housewife: 0.1 (0.03, 0.47) Low versus mid socioeconomic level: 7.60 (2.24, 25.77) BC awareness: No knowledge versus knowledge of BSE: 11.51 (5.18, 25.57) Negative versus positive family history: 2.11 (1.10, 4.16) *Mutually adjusted	Delay between presentation and start of treatment >1.7 mo: OR (95% CI) Socioeconomic: Aged >65 versus <45 y: 1.94 (1.36, 2.40) Rural versus urban area of residence: 2.10 (1.18, 4.40) Illiteracy versus secondary/university: 2.70 (1.38, 5.27) Low versus mid socioeconomic level: 2.61 (1.20, 23.17) Health services: Distance to HCP of diagnosis >100 versus <100 km: 2.46 (1.26, 5.20) ≥3 versus <3 consultations before diagnostic one: 11.44 (4.83, 27.08)	Delay between presentation and start of treatment ≥1.7 mo: OR* (95% CI) Socioeconomic: Aged >65 versus <45 y: 2.51 (1.50, 11.42) Illiteracy versus secondary/university: 1.40 (1.12, 6.50) Low versus mid socioeconomic level: 2.59 (1.04, 6.50) Health services: Distance to HCP of diagnosis ≥100 versus 100 km: 2.58 (1.12, 3.56) ≥3 versus <3 consultations before diagnostic one: 11.27 (4.12, 28.34) *Mutually adjusted
El-Shinawi, 2013 [14] (Egypt)	Delay from symptoms recognition to presentation to an HCP BC awareness: Higher awareness of BSE associated with less delay in seeking medical advice (2.9 + 2.3 mo) relative to low awareness (15.5  + 22.6 mo) (P = .04)	n/a	n/a	n/a
Ermiah, 2012 [15] (Lybia)	Delay from symptom recognition to diagnosis >3 mo Socioeconomic: Aged ≥50 versus <50 y: 64% versus 51% (P = .033) Single versus married: 52% versus 56% (P = .6) Housewife versus employed: 61% versus 48% (P = .09) Illiteracy versus literacy: 69% versus 38% (P = .009) Reproductive: Postmenopausal versus premenopausal: 64% versus 50% (P = .05) No versus breastfeeding: 38% versus 58.6% (P = .09) OC use >5 y versus <5 y or no use: 86% versus 53% (P = .04) BC awareness: Positive versus negative family history: 45% versus 57% (P = .3) Positive versus negative history of benign breast disease: 73% versus 52% (P = .03) Knowledge of BSE versus no knowledge: 0% versus 58% (P < .0001) Type of symptoms: Initial symptom being a lump versus being other symptoms: 41% versus 86% (P < .0001)
Landolsi, 2010 [16]† (Tunisia)	Delay from symptoms recognition to presentation at study setting, i.e., to diagnosis 93% delay related to personal reasons: Not aware of disease: 35% Not having practiced BSE: 23.5% Fear of cancer and/or treatment: 14% Financial problems: 14% Others: 13.5% 24% delay related to health services: Wrong reassurance: 47.5% Misdiagnosis: 18%
Mousa, 2011 [17] (Egypt)	Delay from symptoms recognition to first medical consultation >3 mo: OR (95% CI) Socioeconomic: Aged ≥50 versus < 50 y: 1.1; 95% CI: 0.6, 2.1 Urban versus rural residence: 1.3; 95% CI: 0.7, 2.6 ≥Bachelor versus < bachelor education: 0.6 (0.3, 1.2) Type of symptoms: Breast mass versus other first symptom: 2.1 (0.9, 4.8)	Delay from symptoms recognition to first medical consultation >3 mo: OR* (95% CI) Socioeconomic: Aged ≥50 versus < 50 y: 0.9 (0.4, 1.9) Urban versus rural residence: 1.4 (0.7, 2.9) ≥Bachelor versus <bachelor education: 0.6 (0.3, 1.2) Type of symptoms: Breast mass versus other first symptom: 2.1 (0.9, 4.8) *Adjusted for age, residential status, and education	Delay from first medical consultation to arrival at TTC >2 wk: OR (95% CI) Socioeconomic: Aged ≥50 versus < 50 y: 0.6 (0.3, 1.2) Urban versus rural residence: 0.8 (0.4, 1.5) ≥Bachelor versus <bachelor education: 1.2 (0.7, 2.3) Type of symptoms: Breast mass versus other first symptom: 0.8 (0.4, 1.8) Health services–related: First health care provider versus TCC: Primary care: 11.0 (2.9, 41.7) Gynecologist: 9.0 (1.6, 52.3) Medical oncologist: 5.6 (1.0, 30.9) General surgeon: 5.5 (1.7, 18.0) Surgical oncologist: 3.0 (0.7, 13.4) Other: 12.0 (2.2, 66.5) Navigation pathway versus directly to TCC: General surgeon → Surgical oncologist→ TCC: 29.3 (4.6, 184.4) General surgeon → Medical oncologist→ TCC: 6.0 (0.9, 38.1) Primary care→ Others→ TCC: 19.5 (3.7, 102.4)	Delay from first medical consultation to arrival at TTC >2 wk: OR* (95% CI) Socioeconomic: Aged ≥50 versus < 50 y: 0.6 (0.3, 1.4) Urban versus rural residence: 1.1 (0.5, 2.3) ≥Bachelor versus <bachelor education: 1.3 (0.5, 2.9) Type of symptoms: Breast mass versus other first symptom: 1.3 (0.6, 3.1) Health services–related: First HCP versus TCC: Primary care: 12.2 (2.9, 51.0) Gynecologist: 8.6 (1.4, 53.4) Medical oncologist: 8.3 (1.3, 55.0) General surgeon: 7.6 (2.1, 27.6) Surgical oncologist: 3.4 (0.7, 16.0) Other: 11.0 (1.9, 63.3) Navigation pathway versus directly to TCC: General surgeon → Surgical oncologist → TCC: 35.4 (5.3, 237.5) General surgeon → Medical oncologist→ TCC: 8.1 (1.0, 62.2) Primary care→ Others → TCC: 23.2 (4.0, 134.5) *Adjusted for age, residential status, education level, tumor stage, and first symptom
Stapleton, 2011 [9] (Egypt)	Late versus early stage at diagnosis: Mutually adjusted OR (95% CI) >33 wk versus ≤33 delay in seeking treatment: 1.57 (0.76, 3.23) Financial and other constraints Social, financial, and time constrains versus no delay: 1.72 (0.86, 3.46) Type of symptoms: No pain versus no delay: 2.68 (1.18, 6.08) BC awareness: Knowledge of BSE versus no knowledge: 0.24 (0.06, 0.94) Previous CBE versus no previous CBE: 1.00 (0.28, 3.62) Previous mammogram versus no previous mammogram: 2.17 (0.48, 9.72) Health services related: Site of treatment NCI-Cairo versus TCC: 5.05 (1.30, 19.70) Visited versus not visited a second provider: 0.72 (0.30, 1.74) First diagnosed versus not first diagnosed as BC: 0.99 (0.52, 1.89) Referral versus no referral: 1.10 (0.57, 2.12) Treated in a hospital versus present facility: 0.80 (0.43, 1.48) Travel time to facility >1 h versus ≤1 h: 1.64 (0.96, 2.79)
Sub-Saharan Africa
Clegg-Lamptey, 2009 [18] (Ghana)	Reasons for delay from symptoms recognition to presentation at the study hospital where diagnosis was made (%) Lack of BC awareness: 28.8% Fear of diagnosis or mastectomy: 34.8% Tried traditional/alternative treatments: 19.7% Tried spiritual cures: 19.7% Financial problems: 18.2% Lack of knowledge of BSE: 57.6% Other: 4.5% Health services related: Previous medical consultation: 39.4% Previous hospital consultations at a different hospital: 72.7%, with diagnosis made in only 52% of these
Ezeome, 2010 [19] (Nigeria)	Reasons for delay between symptoms recognition and visit to first HCP Symptom(s) not serious/hoping they will resolve: 27.8% Lack of BC awareness: 23.3% Tried traditional/spiritual treatments: 12.6% Financial problems: 13.9% Painless: 12% Fear/refusal of mastectomy: 5.6% Family/social problems: 5.6% Though it was pregnancy/lactation effect: 3.2% Discouraged by friends/relatives: 3.2% Others: 15.7%	n/a	Reasons for delay between symptoms recognition and start of BC treatment Patient-related Lack of BC awareness: 25.3% Finance: 16.9% Thought it was harmless/will disappear: 15.4% Fear/refused surgery/mastectomy: 9.2% Painless/not disturbing her: 6.9% Delayed by family/social problems: 6.9% Traditional/spiritual treatments: 5.4% Discouraged by friends/relatives: 5.4% Health care provider–related: Delayed referrals or nonreferrals: 17.8% Wrong advice and false reassurance by health professionals: 11.5% Delayed histology report: 6.2% No histology after biopsy: 5.4% Industrial actions: 4.6%	n/a
Ibrahim, 2012 [20] (Nigeria)	Delay from symptoms recognition to first medical consultation >3 mo Reasons given: Lack of BC awareness: 34.1% Belief in spiritual healing: 32.3% Fear of mastectomy: 29.3% Belief in herbal treatment: 22% Belief in alternative therapy: 7.3% Lack of funds: 3% Reassurance by nonmedical health worker: 3% Crude analysis: Being single: OR = 2.05, 95% CI: 0.25, 16.8 Primary level of education: OR = 3.06, 95% CI: 0.96, 9.73 Negative history of benign breast disease: OR = 1.65, 95% CI: 0.76, 3.59	Delay from symptoms recognition to first medical consultation >3 mo “In the multivariate analysis, being premenopausal (OR = 1.86; 95% CI, 0.38, 9.4) was the additional factor associated with increased risk of late presentation” (sic)	n/a	n/a
Marcus, 2013 [21]† (South Africa)	Delay from first symptoms to presentation >6 mo versus 3–6 mo: OR (95% CI) Socioeconomic: Age (vs. 34–45 [sic]): 45–54: 0.15 55–64: 0.18 65–83: 0.77 Education (vs. none): Primary: 0.41 Secondary or higher: 0.18 Employed versus unemployed: 0.26 Married versus single/divorced/widowed: 0.31 BC awareness: Previous cancer diagnosis: 0	Delay from first symptoms to presentation >6 mo versus 3–6 mo: Adjusted* OR (95% CI) Socioeconomic: Age (vs. 34–45 [sic]): 45–54: 2.05 55–64: 2.55 (P < .05) 65–83: 2.28 Education (vs. none): Primary: 0.27 Secondary or higher: 1.56 Employed versus unemployed: 0.63 Married versus single/divorced/widowed: 0.84 BC awareness: Previous cancer diagnosis: 22.13 (P < .01) *for all variables in the model	n/a	n/a
Otieno, 2010 [22]† (Kenya)	Reasons for delays from first symptoms to presentation at diagnostic hospital, i.e., to diagnosis Lack of BC awareness: 7.8% Painless symptom(s): 23.5% Fear of cancer: 19.9% Symptoms considered benign by health professionals: 24.1% Tried traditional treatments: 9.6% Others: 15.1%
Pace, 2015 [23] (Rwanda)	Reasons for delay between first symptoms to first visit to an HCP (%) Did not think it was a problem at first: 76% Thought it would go away: 63% Visited traditional healer first: 21% Thought treatment was too expensive: 14% Too busy at home or job: 7% Fear of cancer: 6% Afraid of treatment and mastectomy: 5%	Reasons for delay between first symptoms to first visit to an HCP: OR* (95% CI) for delay >6 versus <6 mo Socioeconomic: Age (y) versus <40 y: 40–49: 2.26 (0.69, 7.43) 50–59: 1.22 (0.36, 4.11) >60: 2.30 (0.60, 8.74) Married versus unmarried: 1.11 (0.51, 2.48) No education/primary school versus secondary/university: 4.88 (1.72, 13.88) Reproductive: Breastfeeding (yes vs. no): 2.09 (0.44, 9.87) BC awareness: BC family history (yes vs. no): 0.53 (0.14, 2.04) Ever done BSE (yes vs. no): 0.73 (0.31, 1.74) Ever heard of BC (yes vs. no): 1.86 (0.69, 5.00) Type of symptoms and comorbidities: Breast pain as initial symptom (yes vs. no): 0.57 (0.25, 1.30) HIV or other comorbidities (yes vs. no/unknown): 1.15 (0.43, 3.07) Alternative treatments: Saw traditional healer first: 4.26 (1.56, 11.60) Health services related: Travel time to HCP (>2 vs. ≤2 h): 0.96 (0.36, 2.57) Regular CHW visits (yes vs. no): 1.51 (0.66, 3.46) *Mutually adjusted for all variables in the model	Reasons for delay between first visit to an HCP and date of pathology report confirming BC (%) Nonreferral from another health care center: 69% Did not know this cancer existed: 30% Did transfer from another health facility: 27% Too expensive to travel from home to hospital: 21% Told by a health care provider, there was no cure: 3% Hospital too far to travel to: 2%	Reasons for delay between first visit to an HCP and date of pathology report confirming BC OR* (95% CI) for delay ≥6 versus 6 mo Socioeconomic: Age (y) versus <40 y: 40–49: 0.57 (0.20, 1.68) 50–59: 0.85 (0.28, 2.62) >60: 0.64 (0.18, 2.24) Married versus unmarried: 1.11 (0.51, 2.41) No education/primary school versus secondary/university: 1.19 (0.48, 2.97) Reproductive: Breastfeeding (yes vs. no): 0.81 (0.15, 4.30) BC awareness: BC family history (yes vs. no): 0.60 (0.15, 2.34) Ever done BSE (yes vs. no): 1.15 (0.50, 2.65) Ever heard of BC (yes vs. no): 1.19 (0.45, 3.10) Type of symptoms and comorbidities: Breast pain as initial symptom (yes vs. no): 1.15 (0.52, 2.55) HIV or other comorbidities (yes vs. no/unknown): 0.84 (0.32, 2.17) Health services related: Travel time to an HCP (>2 vs. ≤2 h): 1.26 (0.46, 3.42) Regular CHW visits (yes vs. no): 1.14 (0.50, 2.58) No. of visits to other health care facilities before diagnosis (<5 vs. ≥5): 2.69 (1.24, 5.84) Referred by (vs. health center): District hospital: 0.51 (0.09, 2.78) Private hospital: 0.36 (0.06, 2.09) Unknown: 0.49 (0.07, 3.45) *Mutually adjusted for all variables in the model
Price, 2012 [24] (Cameroon)	Financial problems: 16% Spent >$10 on one-way transportation: 42% Traveled >4 h to hospital: 46%		n/a
Toure, 2013 [25] (Côte d’Ivoire)	Reasons for delay between symptoms recognition and date of histological confirmation
	Crude OR (95% CI) for delay > 6 mo Initial symptom (vs. nodule) Inflammation: 23.6 (7.5, 74.0) Ulcer: 18.1 (4.3, 76.9) Nipple discharge: 1.9 (0.6, 6.2) Metastases: 13.9 (3.3, 59.3) Self-reported reason for delay (vs. having financial problems) Traditional medicine: 0.5 (0.2, 1.2) Fear of cancer: 0.4 (0.1, 2.3) Misdiagnosis: 1.8 (0.2, 15.3) Inadequate medical care: 1.1 (0.2, 5.4) Monthly income in euros (vs. none): <91.46: 1.4 (0.5, 3.6) 91.46–182.8: 0.8 (0.3, 2.1) 182.9–274.4: 0.8 (0.3, 2.3) >274.4: 3.2 (0.4, 25.9)		Mutually adjusted OR (95% CI) for delay >6 mo (having financial problems taken as the reference category) Self-reported reason for delay (vs. having financial problems) Traditional medicine: 0.7 (0.7, 3.2) Fear of cancer: 1.2 (0.0, 12.3) Misdiagnosis: 3.0 (0.3, 5.7) Inadequate medical care: 0.6 (0.1, 17.4) Monthly income in euros (vs. none): <91.46: 0.3 (0.0, 1.7) 91.46–182.8: 4.4 (0.2, 91.2) 182.9–274.4: 12.7 (0.4, 376.6) >274.4: 47.8 (0.7, 3.103 [sic])
Quantitative and qualitative studies
Dye, 2010 [26] (Ethiopia)	Reasons for delays between symptom recognition and presentation at diagnostic center (TA) Lack of BC awareness Health services: High travel distance Too expensive >3 HCP visits: 73.2% First HCP: % of patients (Me ± SE number of care nodes visited including study setting [TAH]): Primary care: 53.7% (3.3 ± 1.8) Traditional healer: 16.4% (3.8 ± 0.26) Local/regional hospital: 16.4% (2.3 ± 0.19) Private hospital: 9% (2.8 ± 0.48) TAH: 4.5%
Ly, 2002 [27] (Mali)	Reasons for delays between symptom recognition and presentation at first HCP Symptom(s) not serious: 82% Caused by witchcraft: 14%		n/a
Qualitative studies
Ekortarl, 2007 [28] (Cameroon)	Reasons for delays between symptom recognition and presentation at first HCP Ignorance and beliefs Fears Financial problems Inadequate diagnosis by general doctors
Mbuka-Ongona, 2012 [29] (Botswana)	Reasons for delays between symptom recognition and visit to diagnostic center Lack of BC awareness Misinterpretation of signs Infrequent BSE Fear of diagnosis and death Influence of traditional healers Health services: Poor clinical practices of health workers Overemphasis on HIV infection Long travel distance to hospital
Pruitt, 2015 [30] (Nigeria)	Reasons for delays between symptom recognition and first visit to an HCP Lack of BC awareness Symptom(s) not serious Tried traditional and spiritual treatments		Reasons for delays between presentation and diagnosis and treatment Inappropriate medical care given Delays in getting diagnostic confirmation or treatment Return to traditional care Denial Fear of surgery Strikes by hospital staff Treatment costs

BC = breast cancer; BSE = breast self-examination; CBE = clinical breast examination; CHW = community health worker; CI = confidence interval; HCP = health care provider; HIV = human immunodeficiency virus; IQR = interquartile range; km = kilometers; LABC = locally advanced breast cancer; Md = mean; Me = mean; n/a = not reported in the original publication; OC = oral contraceptives; OR = odds ratio; Ra = range; SE = standard error; TAH = Tikur Anbessa Hospital; TCC = Tanca Cancer Center.

Bold values are statistically significant.

^†Study recruited only patients with advanced breast cancer (see Table 1).