|Year : 2020 | Volume
| Issue : 2 | Page : 65-71
Breast cancer in western part of Libya: Pattern and management (2003-2018)
Eman Gusbi1, Nada Elgriw1, Shiaa Zalmat2, Hafsa Alemam1, Sumia Khalil2, Mokhtar Gusbi3, Miluda Elhamadi3, Taha Benyasaad2, Nabil Enattah1, Adam Elzagheid1
1 Biotechnology Research Center, University of Tripoli, Libya
2 Tripoli Medical Center, University of Tripoli, Libya
3 Department of Family and Community Medicine, Faculty of medicine, University of Tripoli, Libya
|Date of Submission||07-Feb-2020|
|Date of Acceptance||03-Apr-2020|
|Date of Web Publication||22-May-2020|
Prof. Adam Elzagheid
Department of Genetic Engineering, Biotechnology Research Center, Tripoli
Source of Support: None, Conflict of Interest: None
Background: Breast cancer is the second most common cancer in the world; the most frequent cancer among women, and leading cause of cancer death in females worldwide. Aim: The aim of the study is to study the pattern and treatment modalities for breast cancer patients who registered in Tripoli University Hospital from 2003 to 2018. Patients and Methods: A retrospective, cross-sectional study was conducted at the Oncology Department of Tripoli University Hospital. A convenience sample of 1000 breast cancer patients from 2003 to 2018 was chosen. Demographic, clinic-pathological characteristics, and treatment modalities data were analyzed by SPSS program version 20. Results: Of 1000 breast cancer patients, there were 984 (98.4%) females and 16 (1.6%) males, mean age was 46.1 ± 11.7 years old, most of them from western region. Majority (64.3%) of female were early age at menarche and 46.2% not breastfed. Positive family history of first degree was 28.8%. The left side presentation was the predominant (60.3%); half of the cases were in Stage II. Invasive ductal carcinoma was diagnosed among 62.5% of the cases and 47% of them were in Grade III. Positive estrogen receptor recorded in 73.8% of cases compared to 69.5% positive progesterone. Furthermore, 76.8% of patients had human epidermal growth factor receptor 2 negative and 78.4% of cases had high Ki-67 level. Regarding management, a combination of surgery, radiation, chemotherapy, and hormonal were provided to 58% of cases, 45.5% of patients who received chemotherapy were treated with FEC regimen. Hormonal therapy was given to 67.7% and tamoxifen is the most drugs used. Conclusions: The frequency is higher among younger age (<50 years), early age at menarche, breastfed less than a year, nearly half presented in late Stage (III, IV), invasive ductal carcinoma is predominant histopathological type, most cases were HER2 negative and high Ki-67 expression. More efforts toward primary prevention and early detection are recommended to reduce locally advanced breast cancer.
Keywords: Breast cancer, clinical, demography, histopathology, Libya, treatment
|How to cite this article:|
Gusbi E, Elgriw N, Zalmat S, Alemam H, Khalil S, Gusbi M, Elhamadi M, Benyasaad T, Enattah N, Elzagheid A. Breast cancer in western part of Libya: Pattern and management (2003-2018). Libyan J Med Sci 2020;4:65-71
|How to cite this URL:|
Gusbi E, Elgriw N, Zalmat S, Alemam H, Khalil S, Gusbi M, Elhamadi M, Benyasaad T, Enattah N, Elzagheid A. Breast cancer in western part of Libya: Pattern and management (2003-2018). Libyan J Med Sci [serial online] 2020 [cited 2020 Sep 18];4:65-71. Available from: http://www.ljmsonline.com/text.asp?2020/4/2/65/284691
| Introduction|| |
Breast cancer is the most frequent cancer among women, impacting 2.1 million women each year, and it is the leading cause of cancer death in women (15.0%). In 2018, it is estimated that 627,000 women died from breast cancer. While breast cancer rates are higher among women in more developed regions, rates are increasing in nearly every region globally.,,
However, it is incidence varies from countries of high incidence including Northern America, Australia/New Zealand, and Northern and Western Europe; to intermediate in Central and Eastern Europe, Latin America, and the Caribbean; and low rate in most of Africa and Asia.,,
In Eastern Mediterranean regions, the incidence rate noticed obvious rise and the frequencies higher of younger ages and advanced stages at the time of presentation.
In Northern Africa, the data of the regional registries of Algeria, Morocco, and Tunisia show that breast cancer is the most common cancer in women representing 25% of all cancers, which is similar to the frequency in Libya (25.6%).,,
The incidence of breast cancer in Arab countries is significantly lower than that in Western nations. But has been rising, this increase in the incidence contributed to many factors including lifestyle changes that adopted by Arab women, such as late marriage, delayed first pregnancy, having fewer children, taking oral contraceptives, lack of physical activity, obesity, and smoking. Also possible that this increase is partly due to improved detection and diagnosis in some Arab countries and population growth and aging.,,
Breast cancer has different histopathological and biological features that lead to different treatment responses and needs different therapeutic strategies.
Early detection of breast cancer makes higher survivals rates, increased treatment options, and improved quality of life.
The information regarding distribution and the burden of breast cancer is essential for preventive strategy and help in assessing intervention measures, there for the current study was conducted aiming to study the pattern and treatment modalities for breast cancer patients who registered in Tripoli university hospital from 2003 to 2018.
| Patients and Methods|| |
The study was a descriptive, retrospective cross-sectional type, conducted at the Pathology and Oncology Departments of Tripoli University Hospital, Libya, which is a tertiary referral center for breast cancer patients and has the largest data records of breast cancer cases in the country. A convenience sample of 1000 file records of breast cancer patients who registered in the hospital from 2003 to 2018 was selected. Inclusion criteria were all Libyan patients who were registered during the study in Tripoli University Hospital as a case of breast cancer, male and female, any ages and confirmed diagnosis of breast cancer by histopathology. The following conditions were excluded: Non-Libyan patients and all those whose file records deficient in eligible information.
Demographic, clinical, pathological, and biological information including: sex, age at diagnosis, marital status, occupation, residence, family history, age at menarche, parity, duration of breastfeeding, data on use of oral contraceptives and hormonal replacement therapy, histopathological details as type, grade, tumor, node, metastasis staging, biomarkers (estrogen receptor [ER], progesterone receptor [PR], proliferation (Ki67) status, and human epidermal growth factor receptor 2 (HER2) status), and treatment modalities received (surgical, chemotherapy, radiotherapy, hormonal, and targeted therapy) were extracted from medical file records.
The staging of disease during presentation was assessed according to the American Joint Committee on cancer criteria.
Cases with ≥15% positive nuclei were classified as high Ki-67 expression and those with <15% were classified as low Ki-67expression. HER2 was considered positive when the score was +3.
Collected data were sorted, coded, and analyzed by IBM SPSS Statistics for Windows, version 20 (IBM Corp., Armonk, N.Y., USA). Descriptive statistics including frequency, percentage, and mean ± standard deviation, were obtained for all variables as appropriate. Categorical data were compared using Chi-square test and Fisher's exact test if appropriate. Quantitative data were compared using student t-test. A P < 0.05 was considered statistically significant.
Ethical approval was obtained from Biotechnology Research Center Ethical Committee (BEC-BTRC 18-2019).
| Results|| |
The profiles of 1000 cases with breast cancer were evaluated, the results showed that 98.4% were female, their mean age was 46.1 ± 11.7 years old, range (17–79 years), and 1.6% were male with mean age of 45.5 ± 12.9 years, range (19–69 year). Majority of cases (61.8%) were between 35 and 54 years old. The results revealed that 84.4 of 100000 women aged between 35 and 44 years and 194.6 of 100000 women aged between 45 and 54 years were diagnosed with breast cancer. As regards the marital status, 78.6% of patients were married, and 82.1% from western region and more than the half were employment. The family history of breast cancer was reported in 288 patients (28.8%); 220 of them (76.4%) had an affected first-degree relative [Table 1]. The results revealed that 84.4 of 100000 women aged between 35 and 44 years and 194.6 of 100000 women aged between 45 and 54 years were diagnosed with breast cancer [Table 2].
|Table 1: Demographic characteristics of study population according to sex|
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|Table 2: Demonstrates the frequency of the cancer cases and age-standardized rates per 100,000 person per year, for each age group during the study|
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Majority (64.3%) of female cases reported early age at menarche (<12 years) [Figure 1].
More than half of the patients were had ≥4 children [Figure 2] and 455 patients (46.2%) had no breastfeeding, 162 patients (16.5%) were breastfed for 12 months or more [Figure 3].
Oral contraceptive use and hormonal treatment were reported in 62% female patients.
The left side involvement was predominant among males (81.2%) and represents 60% of female cases; while bilateral presentation had occurred only in 32 patients (3.2%), all are females. The most common histological type determined microscopically was invasive ductal carcinoma 625 patients (62.5%), followed by invasive lobular carcinoma (197 patients, 19.7%). Regarding tumor grade, 438 patients (4.8%) were in Grade II, 470 patients (47%) in Grade III. According to the AJCC system, the frequencies were 87 (8.7%), 504 (50.4%), 327 (23.7%), and 82 (8.2%) for Stages I, II, III, and IV, respectively [Table 3].
|Table 3: Clinicopathological characteristics of the cases according to gender|
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A positive ER (ER+) was reported in 87.5% of male cases compared to 73.6% of female patients; PR positive (PR+) in 43.8% of male and 69.9% of females. Furthermore, 76.8% of cases were HER2 negative, only 12.5% of males and 22.9% of female cases had HER2 +3. Ki-67 level ≥15% was recorded among 69% of males and 78.6% of females [Table 4].
|Table 4: Immunohistochemistry markers distribution among breast cancer patients|
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Concerning management, 26.1% of the patients had undergone breast conserving surgery and 73.9% of the patients had done modified radical mastectomy. Vast majority of patients 951 (95.1%) had received radiotherapy, 90.6% received chemotherapy, 45.5% of patients who received chemotherapy were treated with FEC (5-fluorouracil, epirubicin, cyclophosphamide) regimen, and 38.5% with Taxol. and hormonal therapy was given to 67.7% of patients and tamoxifen is the most drugs used. One-third patients had received trastuzumab (43.7% of males and 33.3% of females) [Table 5] and [Table 6].
A combination of surgery, radiation, chemotherapy, and hormonal was provided to 58% of cases [Figure 4].
| Discussion|| |
Breast cancer is the most common cancer in women worldwide. Prediction of this disease depends on various factors such as histological type, grade, size of tumor, lymph node metastasis, and hormone status of the tumor.
In the present study, most of the cases were between 35 and 54 years old, in accordance with results of other studies, which have stated that breast cancer occurs a decade earlier compared to women of western countries;, and the mean age was 46 ± 11.7, which is not different from previous Libyan study., Very young age <35 years represent 17% compared with study done in Egypt (8.19%).
Most of the cases were from Tripoli and AL-jabal Garbi and scanty of cases were from eastern region probably due to the presence of Benghazi medical center which is the referral center for that region. The results of this study revealed that 28.8% of patients had family history, which is higher than reported by Farahat et al., in Egypt (4.7%) as well as by Feng et al. (10%–20%).
Almost (78.6%) of patients were married and according to some studies, being married can have a positive effect on the early diagnosis, treatment, and survival of breast cancer., Breast feeding may lower breast cancer risk, especially if continued for 1.5–2 years. In the present study, 46.2% of the cases had not breastfed their children and only 1.9% of patients were breastfed more than 1 year.
One of the risk factors of breast cancer is long time fertility that happens with menarche at early ages and menopause in old ages. In the current study, most of cases had early age at menarche <12 years old. A relative excess incidence of left over right breast cancer has been well documented in the literature,, which is in agreement with present study finding.
In the current study, most of the tumors (62.5%) were ductal carcinoma, which is in accordance with that reported by Engstrom et al., which revealed 70% of cancers were duct carcinoma, 13.6% were lobular carcinoma and Truin et al. results. The frequency of invasive ductal cancer is higher in men (87.5%) as compared to women (62%), lobular breast carcinoma in men is extremely rare, this is due to the fact that the male breast tissue remains rudimentary and lobular differentiation is uncommon in male breast tissue.
Tumor stage is considered as an important factor in local and distal recurrences, survival rate, and having an effective early diagnosis program. About half of the tumors in present study had been detected in Stage II, 27.1% in Stage IIB, which in agreement with the results reported by Boder et al., that revealed the majority of Libyan breast cancer patients were in Stages IIB and IIIA; the current results showed 40.9% of cases were already at Stage III or IV at presentation and in accordance with the results presented by Yalazal et al., as well as with Malvia et al. study results in India that showed 45.7% where in advanced stages.
Concerning the grade of tumor in the present study, results illustrated that 49.6% of tumors were in Grade 3 or 4 compared with study done by Engstrom et al. revealed that Of the 909 tumors, 12.9% were Grade 1, 53.7% Grade 2, and 33.4% Grade 3.
Tumors with both ER and PR negative have relatively poorer prognosis than cancers with either ER or PR positivity. The main factor in planning of breast cancer treatment is hormone receptor status, ER+, PR+, HER2-tumors have the best prognosis and response to hormone therapy. ER-PR-HER2 + and ER-PR-HER2-tumors are poorly differentiated, show aggressive behavior and poor outcome, and are least likely to respond to hormone therapy.
In this study, 73.8% were positive for ER and 69.5% were positive for progesterone receptor, which is similar to Kadavaret al. results in Iran. Comparing with a study conducted in Pakistan, ER+ cases were 62%, PR+ cases were 47%, and HER2-positive cases were 49%.
Breast cancers with HER2 protein over expression or HER2 gene amplification are called HER2-positive. HER2-negative breast cancers tend to grow less quickly and are less likely to spread and come back compared to HER2-positive breast cancers, which is associated with a poorly differentiated tumor, less hormone receptor expression, high proliferation ability, positive lymph node, and a higher risk of recurrence; HER2 is also considered as prognostic and predictive factor for breast cancer. In this study, HER2 + 3 was 22.7%, when comparing current study results with previous studies in different countries, HER2 + 3 frequency is higher than other countries (10%–15%).,,
Ki-67 level considered a valuable biomarker in breast cancer patients and be used in treatment and follow-up. Patients with Ki-67 >15% are more likely to develop recurrence and distant metastasis than those with Ki-67 <15%. Higher levels of Ki-67 correlate with more rapid tumor growth and tumor aggressiveness in the present study Ki-67 level ≥15% was recorded in 78.4% of the cases, with further analysis 83% of the cases of high Ki-67 where had distal metastasis.
The management of breast cancer is multi-disciplinary with different approaches in nature; and the key determinant of breast cancer outcome is the degree to which newly diagnosed cancers are treated correctly in a proper time.,,
The most appropriate treatment is based on the tumor burden/location (size and location of primary tumor, number of lesions, and extent of lymph node involvement) and biology (pathology, including biomarkers and gene expression), as well as the age, menopausal status, general health status, and preferences of the patient.,
Breast conserving treatment was done for 26.1% of the patients, while 73.9% of cases were underwent radical mastectomy, comparing with Surakasulaet al. results 95% of patients underwent radical mastectomy.
Radiotherapy and chemotherapy were at higher frequency (95.1%, 90.6%), comparing with England study where, radiotherapy 63% (44.7% of males and 63.1% of females) and chemotherapy 34.1% (28.2% of males and 34.2% of females), which can be contributed to advance cancer presentation in our patients.
Most drugs used in the current study was FEC (5 fluorouracil, epirubicin, cyclophosphamide) (45.5%), followed by 38.8% with Taxol, CAF 34.9% and adriamycin, cyclophosphamide (AC) 14.4%. Which was in agreement with Kumar study where majority (59.1%) of patients were treated with anthracycline-based regimen. However, contradicted finding was demonstrated by Surakasuta, where 79% of the cases received AC based chemotherapy.
Hormonal treatment was prescribed to 67.7% of patients, tamoxifen was the most commonly prescribed drug (41.5%), letrozole (Femara), goserelin (Zoladex), and exemestane (Aromasin) were prescribed to 33.8%, 24.4%, and 1.1% of patients, respectively. Compared to a study conducted by Kumaret al. were tamoxofen (79.3%), latrezol 4.5%, and exemestane (0.1%).
Targeted therapy against anti-HER-2 is very effective in tumors that over express HER-2, in the present study Herceptin (Trastuzumab) was received by 33.5% of patients (43.7% of males and 33.4% of females).
The current study has the usual limitation of descriptive epidemiology, that is, retrospective registry assessment, and presence of missing data.
| Conclusions|| |
Breast cancer in Libya is the most frequent cancer among women and is rare in males. Frequency is higher among younger age (<50 years), early age at menarche, breastfed less than a year, nearly half presented in late Stage (III, IV), invasive ductal carcinoma is predominant histopathological type; most cases were HER2 negative and Ki-67 nuclear positivity of more than 15%. Male compared with female breast cancer have higher stage, lower grade, and more ER + tumors. Most of the patients underwent radical mastectomy, received chemotherapy and radiotherapy, two-third received hormonal therapy and one-third targeted therapy.
Improvements in public awareness, lifestyle change, screening programs establishment, improving access to affordable treatment, and more palliative care, support for breast cancer research, are all important measures that need to be addressed to reduce morbidity and mortality.
The authors would like to thank Mr. Walid Mohamed Elmahdi Benbubaker for his assistance in statistical analysis. The authors gratefully acknowledge the support of the Libyan Authority for Research, Science, and Technology by a research grant for this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Moore RS. Impact of culture, education and socio-economic status. In Breast cancer in Women of African Descent, Wiliams C, Olopade O, Falkson C, eds. Springer, Dordrecht: Netherlands; 2006. p. 313.
Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Cancer Res 2004;6:229-39. https://doi.org/10.1186/bcr932
Alwan N. Iraqi initiative of a regional comparative breast cancer research project in the Middle East. J Cancer Biol Res 2014;1:1016.
Belkacemi Y, Tsoutsou PG, Boussen H, Geara F, Bounedjar A, Benider A, et al
. Epidemiology of breast cancer in young women in the southern part of the Mediterranean Area. J Can Epi Treat 2017;4:1-7. Doi: https://doi.org/10.24218/jcet.2017.16
National Cancer Institute. Cancer Registry Department. Annual Report 2014. Sabratha. Libya; 2014. p. 25-31.
Najjar H, Easson A. Age at diagnosis of breast cancer in Arab nations. Int J Surg 2010;8:448-52. doi:10.1016/j.ijsu.2010.05.012.
Hashim MJ, Al-Shamsi FA, Al-Marzooqi NA, Al-Qasemi SS, Mokdad AH, Khan G. Burden of Breast Cancer in the Arab World: Findings from Global Burden of Disease, 2016. J Epidemiol Glob Health 2018;8:54-8. doi:10.2991/j.jegh.2018.09.003.
De Cicco P, Catani MV, Gasperi V, Sibilano M, Quaglietta M, Savini I. Nutrition and Breast Cancer: A Literature Review on Prevention, Treatment and Recurrence. Nutrients 2019;11:1514. doi:10.3390/nu11071514.
Setyawati Y, Rahmawati Y, Widodo I, Ghozali A, Purnomosari D. The Association between Molecular Subtypes of Breast Cancer with Histological Grade and Lymph Node Metastases in Indonesian Woman. Asian Pac J Cancer Prev 2018;19:1263-8. Doi:10.22034/APJCP.2018.19.5.1263.
World Health Organization. Early Detection. Cancer Control: Knowledge into Action: WHO Guide for Effective Programs; Module 3. Switzerland: World Health Organization; 2007. p. 15.
Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A, eds. AJCC Cancer Staging Manual. 7th
ed. New York, USA: Springer, 2010. p. 345-76.
Engstrøm MJ, Opdahl S, Hagen AI, Romundstad PR, Akslen LA, Haugen OA, et al
. Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients. Breast Cancer Res Treat 2013;140:463-73. doi: 10.1007/s10549-013-2647-2.
Rosai J. Breast. In: Rosai and Ackerman's Surgical Pathology. 10th ed. St. Louis: Mosby; 2011. p. 1659-770.
Haghighat S, Akbari ME, Ghaffari S, Yavari P. Standardized breast cancer mortality rate compared to the general female population of Iran. Asian Pac J Cancer Prev 2012;13:5525-8. doi:10.7314/apjcp.2012.13.11.5525.
Malvia S, Bagadi SA, Dubey US, Saxena S. Epidemiology of breast cancer in Indian women. Asia Pac J Clin Oncol 2017;13:289-95. doi:10.1111/ajco.12661.
Boder JM, Elmabrouk Abdalla FB, Elfageih MA, Abusaa A, Buhmeida A, Collan Y. Breast cancer patients in Libya: Comparison with European and central African patients. Oncol Lett 2011;2:323-30. doi:10.3892/ol.2011.245.
Ermiah E, Abdalla F, Buhmeida A, Larbesh E, Pyrhönen S, Collan Y. Diagnosis delay in Libyan female breast cancer. BMC Res Notes 2012;5:452. doi:10.1186/1756-0500-5-452.
Farouk O, Ebrahim MA, Senbel A, Emarah Z, Abozeed W, Seisa MO, et al
. Breast cancer characteristics in very young Egyptian women ≤35 years. Breast Cancer (Dove Med Press) 2016;8:53-8. doi: 10.2147/BCTT.S99350.
Farahat TM, Abd El-Bary NM, Shaheen HM, Khalil NA, Hussein YH. Patients with breast cancer: Screening of the disease among their families in Menoufia University Hospital, Egypt. Menoufia Med J 2019;4:1470-5.
Feng Y, Spezia M, Huang S, Yuan C, Zeng Z, Zhang L. et al
. Breast cancer development and prognosis: Risk factor, cancer stem cells, signaling pathway, genomics, and molecular pathogenesis. Genes āDis 2018;2:77-106.
Martínez ME, Unkart JT, Tao L, Kroenke CH, Schwab R, Komenaka I. et al
. Prognostic significance of marital status in breast cancer survival: A population-based study. PLoS One 2017;12:e0175515. doi:10.1371/journal.pone.0175515.
Aizer AA, Chen MH, McCarthy EP, Mendu ML, Koo S, Wilhite TJ, et al
. Marital status and survival in patients with cancer. J Clin Oncol 2013;31:3869-76.
Ghoncheh M, Pournamdar Z, Salehiniya H. Incidence and Mortality and Epidemiology of Breast Cancer in the World. Asian Pac J Cancer Prev 2016;17:43-6.
Cheng SA, Liang LZ, Liang QL, Huang ZY, Peng XX, Hong XC, et al
. Breast cancer laterality and molecular subtype likely share a common risk factor. Cancer Manag Res 2018;10:6549-54. doi:10.2147/CMAR.S182254.
Amer MH. Genetic factors and breast cancer laterality. Cancer Manag Res 2014;6:191-203. doi:10.2147/CMAR.S60006.
Truin W, Roumen RMH, Siesling S, van de Vijver KK, Tjan-Heijnen VCG, Voogd AC. Estrogen and progesterone receptor expression levels do not differ between lobular and ductal carcinoma in patients with hormone receptor-positive tumors. Breast Cancer Res Treat 2017;164:133-8. doi:10.1007/s10549-017-4220-x.
Yalaza M, İnan A, Bozer M. Male Breast Cancer. J Breast Health 2016;12:1-8. doi:10.5152/tjbh.2015.2711.
Dai X, Xiang L, Li T, Bai Z. Cancer Hallmarks, Biomarkers and Breast Cancer Molecular Subtypes. J Cancer 2016;7:1281-94. doi:10.7150/jca.13141.
Kadivar M, Mafi N, Joulaee A, Shamshiri A, Hosseini N. Breast cancer molecular subtypes and associations with clinicopathological characteristics in Iranian women, 2002- 2011. Asian Pac J Cancer Prev 2012;13:1881-6. doi:10.7314/apjcp.2012.13.5.1881.
Ali A, Ahmad M, Javeed N, Ijaz M, Khan MM, Khattak R, et al
. Clinical and histopathological parameters of the patients with breast cancer from North West Pakistani Population. JIIMC 2017;12:208-12.
Hunt KK, Robertson JF, Bland KI. The breast. In: Schwartz Principles of Surgery. vol. 1., 10th
ed. New York: McGraw-Hill; 2015.
DeSantis CE, Fedewa SA, Goding Sauer A, Kramer JL, Smith RA, Jemal A. Breast cancer statistics, 2015: Convergence of incidence rates between black and white women. CA Cancer J Clin 2016;66:31-42. doi:10.3322/caac.21320.
Lord SJ, Bernstein L, Johnson KA, Malone KE, McDonald JA, Marchbanks PA, et al
. Breast cancer risk and hormone receptor status in older women by parity, age of first birth, and breastfeeding: A case-control study. Cancer Epidemiol Biomarkers Prev 2008;17:1723-30. doi:10.1158/1055-9965.EPI-07-2824.
Collaborative Group on Hormonal Factors in Breast Cancer. Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50302 women with breast cancer and 96973 women without the disease. Lancet 2002;360:187-95. doi:10.1016/S0140-6736(02)09454-0.
Soliman NA, Yussif SM. Ki-67 as a prognostic marker according to breast cancer molecular subtype. Cancer Biol Med 2016;13:496-504. doi:10.20892/j.issn.2095-3941.2016.0066.
Sauter ER. Reliable Biomarkers to Identify New and Recurrent Cancer. Eur J Breast Health 2017;13:162-7. doi:10.5152/ejbh.2017.3635.
World Health Organization. Guidelines for Management of Breast Cancer. EMRO Technical Publication Series; 31. 2006. p. 17. Available from: http://www.emro.who.int/dsaf/dsa697.pdf
. [Last accessed on 2019 Sep 12].
Eniu A, Carlson RW, Elsaghir NS, Bines J, Bese NS, Vorobiof D, et al
. Guidelines implementation for breast health care in Low and middle income countries: Treatment resources allocation. Cancer 2008;113 Suppl 8:2269-8.
Surakasula A, Nagarjunapu GC, Raghavaiah KV. A comparative study of pre- and post-menopausal breast cancer: Risk factors, presentation, characteristics and management. J Res Pharm Pract 2014;3:12-8. doi:10.4103/2279-042X.132704.
] [Full text]
Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al
. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2019;30:1194-1220. doi:10.1093/annonc/mdz173.
Kumar S, Shaikh AJ, Rashid YA, Masood N, Mohammed A, Malik UZ, et al
. Presenting features, treatment patterns and outcomes of patients with breast cancer in Pakistan: Experience at a university hospital. Indian J Cancer 2016;53(2):230-234. doi:10.4103/0019-509X.197728
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]