Menstrual and Reproductive Factors and Risk of Breast Cancer in Iranian Female Population: A Systematic Review and Meta‑Analysis

Elham Manouchehri, Ali Taghipour, Vahid Ghavami, Fatemeh Homaei Shandiz, Abbas Ebadi, Robab Latifnejad Roudsari


Background: Breast cancer (BC) is the most frequent cancer in Iranian females. Due to the changes in lifestyle and reproductive risk factors, the BC incidence rate has been rapidly increasing. Knowing risk factors of BC could significantly contribute to improve preventive behaviors. To investigate the relationship between menstrual and reproductive factors and BC in Iranian female population. Methods: Web of Science, PubMed, Scopus, and SID as well as references of included studies were searched. Among relevant published observational studies, 27 studies met the inclusion criteria. Pooled risk estimates for the risk factors were determined using random‑effects models due to the presence of substantial heterogeneity (P < 0.05). Results: All of the selected studies had case– control design. There was a positive relationship between maternal age at first pregnancy and risk of BC (OR = 1.79 95% CI: 1.36–2.35). Also, menopausal status was associated with higher risk of BC (OR = 1.60 95% CI: 1.18–2.17), whereas, there was no association between menarche age and increased risk of BC (OR = 0.55 95% CI: 0.29–1.03). History of abortion (OR = 1.21 95% CI: 0.97–1.5), nulliparity (OR = 1.43 95% CI: 0.89–2.31), and breastfeeding history (OR = 0.68 95% CI: 0.42–1.09) were not associated with BC risk. Conclusions: Our findings suggest that age at the first pregnancy and menopausal status were significantly associated with BC risk among Iranian women, whereas menarche age, nulliparity, and history of breastfeeding were not. In regard to the history of abortion, our findings revealed no association with BC, but in high‑quality studies, this relationship was significant.


Abortion (induced, spontaneous); breast neoplasm; breastfeeding; menopause; reproductive history

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Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA,

Jemal A. Global cancer statistics 2018: GLOBOCAN estimates

of incidence and mortality worldwide for 36 cancers in 185

countries. CA Cancer J Clin 2018;68:394‑424.

Khakbazan Z, Taghipour A, Roudsari RL, Mohammadi E,

Omranipour R. Delayed presentation of self‑discovered breast cancer symptoms in Iranian women: A qualitative study. Asian

Pac J Cancer Prev 2014;15:9427‑32.

Zendehdel M, Niakan B, Keshtkar A, Rafiei E, Salamat F.

Subtypes of benign breast disease as a risk factor for breast

cancer: A systematic review and meta‑analysis protocol. Iran J

Med Sci 2018;43:1‑8.

Manouchehri E, Taghipour A, Ghavami V, Ebadi A, Homaei F,

Roudsari RL. Night‑shift work duration and breast cancer risk:

An updated systematic review and meta‑analysis. BMC Womens

Health 2021;21:1‑16.

Karim SM, Baeshen W, Neamatullah SN, Bin B. Oral

contraceptives, abortion and breast cancer risk: A case control

study in Saudi Arabia. Asian Pac J Cancer Prev 2015;16:3957‑60.

Mehdipour P, Pirouzpanah S, Kheirollahi M, Atri M. Androgen

receptor gene CAG repeat polymorphism and breast cancer risk

in Iranian women: A case‐control study. Breast J 2011;17:39‑46.

Parsa P, Parsa B. Effects of reproductive factors on risk of

breast cancer: A literature review. Asian Pac J Cancer Prev


Inumaru LE, Irineu Gomes Duarte Quintanilha M, Aparecida da

Silveira É, Veloso Naves MM. Risk and protective factors for

breast cancer in Midwest of Brazil. J Environ Public Health

doi: 10.1155/2012/356851.

Hosseinzadeh M, Eivazi Ziaei J, Mahdavi N, Aghajari P,

Vahidi M, Fateh A, et al. Risk factors for breast cancer in Iranian

women: A hospital‑based case‑control study in Tabriz, Iran.

J Breast Cancer 2014;17:236‑43.

Dianatinasab M, Fararouei M, Mohammadianpanah M,

Zare‑Bandamiri M, Rezaianzadeh A. Hair coloring, stress, and

smoking increase the risk of breast cancer: A case‑control study.

Clin Breast Cancer 2017;17:650‑9.

Ebrahimi M, Vahdaninia M, Montazeri A. Risk factors for

breast cancer in Iran: A case‑control study. Breast Cancer Res


Montazeri A, Jarvandi S, Ebrahimi M, Haghighat S, Ansari M.

The role of depression in the development of breast cancer:

Analysis of registry data from a single institute. Asian Pac J

Cancer Prev 2004;5:316‑9.

Youlden DR, Cramb SM, Yip CH, Baade PD. Incidence and

mortality of female breast cancer in the Asia‑Pacific region.

Cancer Biol Med 2014;11:101‑15.

Akbari A, Khayamzadeh M, Salmanian R, Motlagh AG,

Roshandel G, Nouri M, et al. National Cancer

Mortality‑to‑Incidence Ratio (MIR) in Iran (2005‑2014). Int J

Cancer Manag 2019;12:e94145.

Jazayeri SB, Saadat S, Ramezani R, Kaviani A. Incidence of

primary breast cancer in Iran: Ten‑year national cancer registry

data report. Cancer Epidemiol 2015;39:519‑27.

Davari M, Yazdanpanah F, Aslani A, Hosseini M, Nazari AR,

Mokarian F. The direct medical costs of breast cancer in Iran:

Analyzing the patient’s level data from a cancer specific hospital

in Isfahan. Int J Prev Med 2013;4:748‑54.

Davari M, Mokarian F, Hoseini M, Aslani A, Nazari A,

Yazdanpanah F. Direct Medical Costs of Breast Cancer in Iran,

Analyzing Patients Level Data from a Cancer Specific Hospital

in Isfahan, Iran. Health Inf. Manag. J. 2013;10:1-10.

Crew KD, Gammon MD, Terry MB, Zhang FF, Zablotska LB,

Agrawal M, et al. Polymorphisms in nucleotide excision

repair genes, polycyclic aromatic hydrocarbon‑DNA adducts,

and breast cancer risk. Cancer Epidemiol Biomarkers Prev


Tazhibi M, Dehghani M, Babazadeh S, Makkarian F,

Tabatabaeian M, Sadeghi M, et al. Hormonal and reproductive

risk factors associated with breast cancer in Isfahan patients.

J Educ Health Promot 2014;3:69.

Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA

group. Preferred reporting items for systematic reviews and

meta‑analyses: The PRISMA statement. Int J Surg 2010;8:336‑41.

McElvenny DM, Crawford JO, Davis A, Dixon K, Alexander C,

Cowie H, et al. A review of the impact of shift‑work on

occupational cancer: Part 1–epidemiological research. Policy

Pract. Health Saf. 2018;16:71‑108.

Tawfik GM, Dila KAS, Mohamed MYF, Tam DNH, Kien ND,

Ahmed AM, et al. A step by step guide for conducting a

systematic review and meta‑analysis with simulation data. Trop

Med Health 2019;47:1‑9.

Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Introduction

to Meta‑Analysis. John Wiley and Sons; 2011. 239‑42 p.

DerSimonian R, Laird N. Meta‑analysis in clinical trials.

Controlled Clinical Trials 1986;7:177‑88.

Borenstein M, Hedges LV, Higgins JP, Rothstein HR. Introduction

to Meta‑Analysis. John Wiley and Sons; 2009. p. 107‑17.

Higgins JP, Thompson SG. Quantifying heterogeneity in a meta‐

analysis. Stat Med 2002;21:1539‑58.

Egger M, Smith GD, Schneider M, Minder C. Bias in

metaanalysis detected by a simple, graphical test. BMJ Open


Begg CB, Mazumdar M. Operating characteristics of

a rank correlation test for publication bias. Biometrics


Duval S, Tweedie R. A nonparametric “trim and fill” method

of accounting for publication bias in meta‑analysis. J Am Stat

Assoc 2000;95:89‑98.

Duval S, Tweedie R. Trim and fill: A simple funnel‐plot–based

method of testing and adjusting for publication bias in meta‐

analysis. Biometrics 2000;56:455‑63.

Ebrahimi M, Montazeri A. Investigating the reproductive risk

factors in patients with breast cancer. Paiesh 2002;1:23‑7.

Razmara L HK, Talaiezadeh AH, Tahmasebi M, Karandish M.

Relationship between fish consumption and decreased breast

cancer risk. Sci Med J 2010;9:307‑16.

Sepandi M, Akrami M, Tabatabaee H, Rajaeefard A,

Tahmasebi S, Angali KA, et al. Breast cancer risk factors

in women participating in a breast screening program:

A study on 11,850 Iranian females. Asian Pac J Cancer Prev


Zare N, Haem E, Lankarani KB, Heydari ST, Barooti E.

Breast cancer risk factors in a defined population: Weighted

logistic regression approach for rare events. J Breast Cancer


Sharifzadeh GhR. HM, Kermani T, Ataiee M, Akhbari SH.

Breast cancer and the related factors: A case control study. J

Birjand Univ Med Sci 2011;17:191‑9.

Hajian‑Tilaki K, Kaveh‑Ahangar T. Reproductive factors

associated with breast cancer risk in northern Iran. Med Oncol


Ghiasvand R, Maram ES, Tahmasebi S, Tabatabaee SHR. Risk

factors for breast cancer among young women in southern Iran.

Int J Cancer 2011;129:1443‑9.

Akbari A, Razzaghi Z, Homaee F, Khayamzadeh M,

Movahedi M, Akbari ME. Parity and breastfeeding are preventive

measures against breast cancer in Iranian women. Breast cancer


Moradinazar M, Marzbani B, Shahebrahimi K, Shahabadi S,

Marzbani B, Moradinazar Z. Hormone therapy and factors

affecting fertility of women under 50‑year‑old with breast cancer. Breast Cancer 2019;11:309‑19.

Mahouri K, Dehghani Zahedani M, Zare S. Breast cancer risk

factors in south of Islamic Republic of Iran: A case‑control

study. East Mediterr Health J 2007;13:1265‑73.

Keihanian Sh GF, Fotookian Z, Shoormij R, Saravi M. To

investigation the cancer risk factors in Ramsar and Tonekabon. J.

Qazvin Univ. Med. Sci. Health Serv. 2010;14:12‑9.

Jafarinia B, Bahadorzai M, Delpisheh A, Sayehmiri K,

Tavakoli M. Risk factors of breast cancer in Dezful city of Iran:

A case‑control study. Tehran Univ Med J 2016;74:135‑9.

Marzbani B, Taymoori P, Nouri B. Assessment of risk factors

for breast cancer among women under 50 years old. Journal of

School of Public Health and Institute of Public Health

Research 2017;15:47‑60.

Zayeri F, Seyedagha S, Aghamolaie H, Boroumand F, Yavari P.

Comparison of the logistic regression and classification tree

models in determining the risk factors and prediction of breast

cancer. Iran J Epidemiol 2016;12:49‑57.

Pesaran Z, Rezaei A, Kia RT, Siydat A. Evaluation of breast

cancer risk factors for using in hormone replacement therapy of

corticosteroid- treated post-menopausal women. J Shahrekord

Univ Med Sci 2003;5:70-5.

Amini Sani N SM, Ehdaeivand F, Mardi A. Investigating the

relationship between abortion and breast cancer risk in women

living in Mashhad: A case control study. Res Scientific J Ardabil

Univ Med Sci health Serv 2003;2:7‑12.

Holakouie Naieni KH, Ardalan A, Mahmoodi M, Motevalian A,

Yahyapoor Y, Yazdizadeh B. Risk factors of breast cancer in

north of Iran: A case‑control in Mazandaran Province. Asian Pac

J Cancer Prev 2007;8:395.

Yavari P, Mosavizadeh M, Sadrol‑Hefazi B, Mehrabi Y.

Reproductive characteristics and the risk of breast cancer‑‑A

case‑control study in Iran. Asian Pac J Cancer Prev 2005;6:370‑5.

Tehranian N, Shobeiri F, Pour FH, Hagizadeh E. Risk factors for

breast cancer in Iranian women aged less than 40 years. Asian

Pac J Cancer Prev 2010;11:1723‑5.

Lotfi M, Charkhati S, Shobeyri S. Breast cancer risk factors in an

urban area of Yazd city, Iran. Acta Med Iranica 2008;46:258‑64.

Joukar F, Ahmadnia Z, Atrkar‑Roushan Z, Hasavari F, Rahimi A.

The investigation of risk factors impacting breast cancer in

Guilan Province. Asian Pac J Cancer Prev 2016;17:4623‑9.

Moosazadeh M, Zaboli E, Alizadeh‑Navaei R, Ranjbaran H,

Amjadi O, Faghih M, et al. Association between anthropometric

indices and breast cancer based on the data of the enrolment

phase (cross‑sectional) in Tabari cohort study: The causal

relationship or violation of temporality. J Mazandaran Univ Med

Sci 2019;29:64‑71.

Zahmatkesh BH, Keramat A, Alavi N, Khosravi A, Chaman R.

Role of menopause and early menarche in breast cancer:

A meta‑analysis of Iranian studies. Nurs Midwifery Stud


Namiranian N, Moradi‑Lakeh M, Razavi‑Ratki SK, Doayie M,

Nojomi M. Risk factors of breast cancer in the Eastern

Mediterranean Region: A systematic review and meta‑analysis.

Asian Pac J Cancer Prev 2014;15:9535‑41.

Besharat S, Motie MR, Besharat M, Roshandel G. Breast cancer

risk factors in women of Golestan Province in Iran: A case‑control

study. Iran J Obstet Gynecol Infertil 2011;13:46‑51.

Jafari‑Mehdiabad F, Savabi‑Esfahani M, Mokaryan F, Kazemi A.

Relationship between breastfeeding factors and breast cancer in

women referred to Seyed Al‑Shohada Hospital in Isfahan, Iran.

Iran J Nurs Midwifery Res 2016;21:622‑7.

Vishwakarma G, Ndetan H, Das DN, Gupta G, Suryavanshi M,

Mehta A, et al. Reproductive factors and breast cancer risk:

A meta‑analysis of case–control studies in Indian women. South

Asian J Cancer 2019;8:80‑4.

Nindrea RD, Aryandono T, Lazuardi L. Breast cancer risk

from modifiable and non‑modifiable risk factors among women

in Southeast Asia: A meta‑analysis. Asian Pac J Cancer Prev


Dogan N, Toprak D. Female breast cancer mortality rates in

Turkey. Asian Pac J Cancer Prev 2014;15:7569‑73.

Kuru B, Ozaslan C, Ozdemir P, Dinç S, Camlibel M,

Alagöl H. Risk factors for breast cancer in Turkish women

with early pregnancies and long‑lasting lactation. Acta Oncol


Albeshan SM, Mackey MG, Hossain SZ, Alfuraih AA,

Brennan PC. Breast cancer epidemiology in gulf cooperation

council countries: A regional and international comparison. Clin

Breast Cancer 2018;18:e381‑92.

Ozsoy A, Barça N, Dolek BA, Aktaş H, Elverici E, Araz L,

et al. The relationship between breast cancer and risk factors:

A single‑center study. Eur J Breast Health 2017;13:145‑9.

Gokdemir‑Yazar O, Yaprak S, Colak M, Yildirim E, Guldal D.

Family history attributes and risk factors for breast cancer in

Turkey. Asian Pac J Cancer Prev 2014;15:2841‑6.

Shamsi U, Khan S, Usman S, Soomro S, Azam I. A multicenter

matched case control study of breast cancer risk factors

among women in Karachi, Pakistan. Asian Pac J Cancer Prev


Gad ZM, Elhafeez SSA, Ghareeb KAH, Shwana S,

Al Talabani BGM, Taha DA, et al. An epidemiological study

of female breast cancer in Sulaymaniyah City, Iraqi Kurdistan.

Tabari Biomed Stu Res J 2020;2:13‑21.

Nojomi M, Mirfakhraee R, Hosseini N. Relationship between

hormonal factors and breast cancer. Hakim Health Syst Res J


Peterson NB, Huang Y, Newcomb PA, Titus‑Ernstoff L,

Trentham‑Dietz A, Anic G, et al. Childbearing recency and

modifiers of premenopausal breast cancer risk. Cancer Epidemiol

Prev Biomarkers 2008;17:3284‑7.

Mao J, Shi J, He S, Li N, Shi J, Yang F. Reproductive factors and

risk of breast cancer: A pooled meta‑analysis of 55 case‑control

studies based on different source populations. Int J Clin Exp

Med 2019;12:6453‑68.

Park B, Park S, Shin H‑R, Shin A, Yeo Y, Choi J‑Y, et al.

Population attributable risks of modifiable reproductive factors

for breast and ovarian cancers in Korea. BMC Cancer 2016;16:5.

Li H, Sun X, Miller E, Wang Q, Tao P, Liu L, et al. BMI,

reproductive factors, and breast cancer molecular subtypes:

A case‑control study and meta‑analysis. J Epidemiol


Alim NE, Kiziltan G. Assessment of risk factors of obesity

and diet on breast cancer in Ankara, Turkey. Pak J Med Sci


Yeganeh Z, Sheikhan Z, Kariman N, Hajian P, Nasiri M,

Mirzadeh N. Relationship between pregnancy‑related variables

and risk of breast cancer: Systematic review. Iran J Obstet

Gynecol Infertil 2018;21:85‑97.

Beral V, Bull D, Doll R, Peto R, Reeves G; Collaborative

Group on Hormonal Factors in Breast Cancer. Breast cancer

and abortion: Collaborative reanalysis of data from 53

epidemiological studies, including 83 000 women with breast

cancer from 16 countries. Lancet 2004;363:1007‑16.

Henderson KD, Sullivan‑Halley J, Reynolds P, Horn‑Ross PL,

Clarke CA, Chang ET, et al. Incomplete pregnancy is not associated with breast cancer risk: The California teachers study.

Contraception 2008;77:391‑6.

Huang Y, Zhang X, Li W, Song F, Dai H, Wang J, et al.

A meta‑analysis of the association between induced abortion

and breast cancer risk among Chinese females. Cancer Causes

Control 2014;25:227‑36.

Brind J, Condly SJ, Lanfranci A, Rooney B. Induced abortion as

an independent risk factor for breast cancer: A systematic review

and meta‑analysis of studies on South Asian women. Issues Law

Med 2018;33:32‑54.

Ozmen V, Ozcinar B, Karanlik H, Cabioglu N, Tukenmez M,

Disci R, et al. Breast cancer risk factors in Turkish women–A

University Hospital based nested case control study. World J

Surg Oncol 2009;7:37.

Deng Y, Xu H, Zeng X. Induced abortion and breast cancer: An

updated meta‑analysis. Medicine 2018;97:e9613.

Guo J, Huang Y, Yang L, Xie Z, Song S, Yin J, et al. Association

between abortion and breast cancer: An updated systematic

review and meta‑analysis based on prospective studies. Cancer

Causes Control 2015;26:811‑9.

ACOG Committee Opinion No. 434: Induced abortion and breast

cancer risk. Obstet Gynecol 2009;113:1417‑8.

National Cancer Institute. Summary report: Early reproductive

events and breast cancer workshop. Issues Law Med 2005;21:161‑5.