2. Methodology

A systematic review literature was conducted between March and April 2017; articles were collected from four databases (Web of Science, MEDLINE, Scopus and CINAHL), as well as from references in published research and reviews. The search strategy for potentially eligible studies included the following MeSH terms and combinations: Breast Feeding and Primary Prevention and Breast Neoplasms. The reference lists of included studies were also searched for additional eligible studies. Article inclusion criteria were as follows: (1) original studies and articles reporting on human females, (2) written in English and published in peer-reviewed journals, and (3) studies conducted in developed countries (Organization for Economic Cooperation and Development countries as defined by the World Bank). The following exclusion criteria were used: (1) studies using qualitative methodology, and (2) studies where analytic methods were not clearly reported. Titles and abstracts of retrieved studies were screened to assess whether inclusion criteria were met. Full texts were assessed when the abstract was found insufficient to make conclusions about inclusion. A total of 48 scientific articles were found, 41 in Web of Science, 2 in MEDLINE, 3 in Scopus, and 2 in CINAHL. Out of potentially relevant citations retrieved from electronic databases and searches of reference lists, finally, 34 articles were selected for this review (Table 1).



such as occupational exposure, rotating shift work and environmental factors (increased atmospheric pollution, sedentary lifestyle, and inadequate nutritional habits combined with an unbalanced diet). Other risk factors to be considered are lower age at menarche (below 10 years), late maternal age at first full-term pregnancy (over the age 30–40 years), and short periods of

In the last years, different breast cancer prevention studies have been carried out internationally. Their main objective was to evaluate how a woman's chance of developing breast cancer was affected by breastfeeding as well as by pregnancy and childbirth. The results of these studies provide evidence about the influence of hormonal and reproductive factors in the

A systematic review literature was conducted between March and April 2017; articles were collected from four databases (Web of Science, MEDLINE, Scopus and CINAHL), as well as from references in published research and reviews. The search strategy for potentially eligible studies included the following MeSH terms and combinations: Breast Feeding and Primary Prevention and Breast Neoplasms. The reference lists of included studies were also searched for additional eligible studies. Article inclusion criteria were as follows: (1) original studies and articles reporting on human females, (2) written in English and published in peer-reviewed journals, and (3) studies conducted in developed countries (Organization for Economic Cooperation and Development countries as defined by the World Bank). The following exclusion criteria were used: (1) studies using qualitative methodology, and (2) studies where analytic methods were not clearly reported. Titles and abstracts of retrieved studies were screened to assess whether inclusion criteria were met. Full texts were assessed when the abstract was found insufficient to make conclusions about inclusion. A total of 48 scientific articles were found, 41 in Web of Science, 2 in MEDLINE, 3 in Scopus, and 2 in CINAHL. Out of potentially relevant citations retrieved from electronic databases and searches of reference lists, finally, 34

breastfeeding [6].

56 Selected Topics in Breastfeeding

2. Methodology

development of breast cancer [7–9].

articles were selected for this review (Table 1).

Pathak DR, Osuch JR, He J. Breast carcinoma etiology:

González-Jiménez E, García PA, Aguilar MJ, Padilla CA,

Álvarez J.

Authors Title Year Design Conclusions

2000 Literature review

2014 Retrospective study of the clinical histories

To promote public health in diverse populations, and to provide further insight into breast carcinoma etiology, research needs to focus on multicultural differences and similarities in the relation of hormonal risk factors and breast carcinoma.

Breastfeeding for over six months not only provides children with numerous health benefits, but also protects mothers from breast cancer

current knowledge and new insights into the effects of reproductive and hormonal risk factors in black and white

populations.

histories.

Breastfeeding and the prevention of breast cancer: a retrospective review of clinical


Authors Title Year Design Conclusions

Lactation history and breast

The association between lactation and breast cancer in an international case–control study: a re–analysis by menopausal status

History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic

literature

cancer risk

Freudenheim JL, Marshall JR, Vena JE, Moysich KB, et al.

Stuver SO, Hsieh CC, Bertone E, Trichopoulos D.

Lipworth L, Bailey LR, Trichopoulos D.

physical activity), familial history of breast cancer, mammographic density, history of benign breast disease, ionizing radiation, bone density, height, IGF-1 and prolactin levels, chemopreventive agents. Additionally, we summarized breast cancer risk associated with the following genetic factors: breast cancer susceptibility high-penetrance genes (BRCA1, BRCA2, p53, PTEN, ATM, NBS1 or LKB1) and low-penetrance genes such as cytochrome P450 genes (CYP1A1, CYP2D6, CYP19), glutathione S-transferase family (GSTM1, GSTP1), alcohol and one-carbon metabolism genes (ADH1C and MTHFR), DNA repair genes (XRCC1, XRCC3, ERCC4/XPF) and genes encoding cell signaling molecules (PR, ER, TNFα or

59

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HSP70).

Breast cancer risk was very weakly associated with long duration of lactation among premenopausal women. Among postmenopausal women, the protective effect of lactation was restricted to women with first lactation before age 25 years.

This study did not suggest a protective effect of lactation among the premenopausal women. Although the 95% confidence intervals around the estimates generated

the possibility of a reduced risk of breast cancer associated with breast-feeding, no consistent dose–response with increasing

do not exclude

duration was evident.

The evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. It

total

1997 Case–control study

Breastfeeding and Reduced Risk of Breast Cancer in Women: A Review of Scientific Evidence

1997 Case–control study

2000 Literature review


Authors Title Year Design Conclusions

2002 Literature review

2012 Retrospective study of the clinical histories

2007 Literature review

2010 Retrospective study of the clinical histories

2003 Prospective study

2000 Case–control study

2005 Literature review

The main risk factors for breast cancer identified by observing patterns of risk among various population groups are age, race/ethnicity, reproductive

menopause, and pregnancy and lactation history), and obesity.

Human milk may confer longterm benefits such as lower risk of certain malignancies. A reduced incidence of breast cancer is best documented.

Breastfeeding for periods of longer than six months, not only provides children with many health benefits, but may also protect the mother from serious diseases, such as breast

This prospective study of a large Korean cohort provides strong empirical evidence that lactation decreases the risk of breast cancer among premenopausal women.

The reduction in risk associated with duration of breastfeeding was not primarily due to breastfeeding the firstborn and more evident in women who were older (> 25 years) when they first breastfed and among women who experienced a recent full-term pregnancy.

Risk factors that modulate the development of breast cancer are: age, geographic location (country of origin) and socioeconomic status, reproductive events, exogenous hormones, lifestyle risk factors (alcohol, diet, obesity and

cancer.

factors (menarche,

Extreme serum levels of estrogen, progesterone and prolactin appear to be related to the early development of breast cancer, which in turn is influenced by the existence of a family history of cancer among those women with normal or average hormone levels.

related risk factors for breast

Influence of nutritional status, hormones serum levels, and family history on breast cancer

Bernstein L. Epidemiology of endocrine-

González-Jiménez E, Garcia-Lopez PA, Schmidt-Rio-Valle J,

58 Selected Topics in Breastfeeding

Løland BF, Baerug AB, Nylander G.

Aguilar Cordero MJ, González Jiménez E, Alvarez Ferre J, Padilla Lopez CA, Mur Villar N, Garcia Lopez

Lee SY, Kim MT, Kim SW,

Chang-Claude J, Eby N, Kiechle M, Bastert G, et al.

PA, et al.

Song MS, et al.

Valenza C.

cancer.

development

Human milk, immune responses and health effects

Breast feeding: an effective method to prevent breast cancer

Effect of lifetime lactation on breast cancer risk: a Korean women's cohort study.

Breastfeeding and breast cancer risk by age 50 among women in

risk–where do we stand in

Germany.

Dumitrescu RG, Cotarla I. Understanding breast cancer

2005?


3. Pregnancy

Awatef M, Olfa G, Imed H,

Galukande M, Wabinga H, Mirembe F, Karamagi C, et al.

Table 1. Summary table of selected studies.

Kacem M, et al.

Nagata C, Mizoue T, Tanaka K, Tsuji I, et al.

Early pregnancy has a protective effect against breast cancer [10]. Some of the mechanisms explaining the protective effect of pregnancy have been explored in animal models of breast cancer. Both early age (less than 20 years versus more than 30 years) at first full-term pregnancy and higher parity decrease breast cancer risk to half of the risk of nulliparous women [10]. Although the mechanisms are not entirely elucidated, pregnancy has been hypothesized to reduce the risk of breast cancer primarily through two mechanisms: firstly estrogen-induced mitosis may be suppressed by estriol, the main estrogen produced during pregnancy. Secondly, estrogen-induced mitosis may be suppressed by the hormone prolactin, whose levels are increased during pregnancy [11]. Then, high levels of estriol may protect women against the development of breast cancer [12, 13]. However, there is somewhat less agreement concerning the role of prolactin in the disease. Different studies show a relationship between hyperprolactinemia and an increased risk of breast cancer in women [14, 15]. The mechanisms potentially involved are: increased synthesis and expression of prolactin receptors in malignant breast tissue and a prolactin-induced increase in DNA synthesis in breast cancer cell in vivo [14]. Secondly, and according to Levine and Dolin [16], pregnancy reduces the risk of breast cancer because of the excretion of lipophilic carcinogens by the mother through the fetal fat and vernix caseosa. Other studies have yielded conflicting results. According to Alberktsen et al. [17] in their study with 802,457 Norwegian women (20–56 years old), an increase in the diagnosis of breast cancer after full-term pregnancy was observed, particularly between 3 and 4 years after the delivery. Hakansson et al. [18] and, more recently, Rough et al. [19] reported that human milk causes the

Authors Title Year Design Conclusions

Breastfeeding reduces breast cancer risk: a case–control study

Breastfeeding and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population.

Breast cancer risk factors among Ugandan women at a tertiary hospital: A case–control

in Tunisia

study.

late age at first birth and abortion were the most important reproductive factors associated with breast cancer

61

http://dx.doi.org/10.5772/intechopen.72688

The results support an inverse association between

breastfeeding and breast cancer

The results suggest that breastfeeding possibly decreases the risk of breast cancer among Japanese women

Breastfeeding seems to be associated with reduced odds of

breast cancer.

risk.

risk.

2010 Case–control study

Breastfeeding and Reduced Risk of Breast Cancer in Women: A Review of Scientific Evidence

2012 Systematic review

2016 Case–control study


Table 1. Summary table of selected studies.

#### 3. Pregnancy

Authors Title Year Design Conclusions

2002 Systematic review and Meta-analysis

2015 Systematic review and Meta-analysis

2012 Case–control study

2000 Literature review

1992 Case–control study

1992 Case–control study

1996 Prospective study

2000 Case–control study

2011 Case–control study

Breast cancer and breastfeeding: collaborative reanalysis of individual data from 47 epidemiological studies in 30 countries, including 50,302 women with breast cancer and 96,973 women without the

Breastfeeding and maternal health outcomes: a systematic review and meta-analysis.

Reproductive and hormonal risk factors for luminal, HER2 overexpressing, and triple negative breast cancer in Japanese women.

History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic

Independent protective effect of lactation against breast cancer: a case control study in Japan.

A case–control study of breast cancer in Tianjin, China.

Prospective assessment of breastfeeding and breast cancer incidence among 89,887 women

Lactation reduces breast cancer risk in Shandong Province,

Reproductive factors associated with breast cancer risk in

literature.

China.

northern Iran

disease.

Collaborative Group on Hormonal Factors in Breast

60 Selected Topics in Breastfeeding

Chowdhury R, Sinha B, Sankar MJ, Taneja S, et al.

Islam T, Matsuo K, Ito H, Hosono S, et al.

Lipworth L, Bailey LR, Trichopoulos D.

Yoo KY, Tajima K, Kuroishi T,

Wang QS, Ross RK, Yu MC,

Michels KB, Willett WC, Rosner BA, Manson JE, et al.

Zheng T, Duan L, Liu Y, Zhang B, et al.

Hajian-Tilaki KO, Kaveh-

Ahangar T.

Hirose K, et al.

Ning JP, et al.

Cancer.

appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women.

The longer women breast feed

breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in

are protected against breast cancer. The lack of or short lifetime duration of

Breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea.

Reproductive events in adolescence have differential impact on the risk of breast cancer molecular subtypes in

The evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer.

Lactation has an independent protective effect against breast cancer in Japanese women.

The results strongly suggest that both parity and lactation independently contribute to breast cancer risk.

The results suggest that there is

no important overall association between breastfeeding and the occurrence of

These results suggest that prolonged lactation reduces breast cancer risk.

The duration of breast feeding was inversely associated with breast cancer risk. Nulliparity,

breast cancer.

Japanese.

the more they

these countries.

Early pregnancy has a protective effect against breast cancer [10]. Some of the mechanisms explaining the protective effect of pregnancy have been explored in animal models of breast cancer. Both early age (less than 20 years versus more than 30 years) at first full-term pregnancy and higher parity decrease breast cancer risk to half of the risk of nulliparous women [10]. Although the mechanisms are not entirely elucidated, pregnancy has been hypothesized to reduce the risk of breast cancer primarily through two mechanisms: firstly estrogen-induced mitosis may be suppressed by estriol, the main estrogen produced during pregnancy. Secondly, estrogen-induced mitosis may be suppressed by the hormone prolactin, whose levels are increased during pregnancy [11]. Then, high levels of estriol may protect women against the development of breast cancer [12, 13]. However, there is somewhat less agreement concerning the role of prolactin in the disease. Different studies show a relationship between hyperprolactinemia and an increased risk of breast cancer in women [14, 15]. The mechanisms potentially involved are: increased synthesis and expression of prolactin receptors in malignant breast tissue and a prolactin-induced increase in DNA synthesis in breast cancer cell in vivo [14]. Secondly, and according to Levine and Dolin [16], pregnancy reduces the risk of breast cancer because of the excretion of lipophilic carcinogens by the mother through the fetal fat and vernix caseosa. Other studies have yielded conflicting results. According to Alberktsen et al. [17] in their study with 802,457 Norwegian women (20–56 years old), an increase in the diagnosis of breast cancer after full-term pregnancy was observed, particularly between 3 and 4 years after the delivery. Hakansson et al. [18] and, more recently, Rough et al. [19] reported that human milk causes the vitro apoptosis or the programmed cell death of several varieties of cancer cells. On the other hand, the decrease of breast cancer risk due to prolonged lactation may be explained in part by the reduction of total number of ovulatory menstrual cycles and consequently cumulative ovarian hormone exposure [20]. Despite the scientific evidence available, there is an important controversy about the effect of hormones on the development of breast cancer. This is a complex task when we consider the complex etiopathogenic nature of breast tumors. Consequently, further studies are necessary in order to analyze this relationship [21].

The decrease of relative risk´ rate of developing breast cancer associated with breastfeeding did not change significantly for women in developed and developing countries, and did not change according to the age and ethnicity [31]. Other studies have analyzed breast cancer risk factors, including breastfeeding duration, in Asian and African populations. The results obtained about breastfeeding duration and risk of developing breast cancer between these

Breastfeeding and Reduced Risk of Breast Cancer in Women: A Review of Scientific Evidence

http://dx.doi.org/10.5772/intechopen.72688

63

Additionally Michels et al. [37], in the Nurse's Health Study, in a retrospective review of breastfeeding duration in nearly 90,000 women, reported that, in comparison to never breastfeeding, the RR was 0.86 for fewer than 3 months of breastfeeding, 0.95 for 7–11 months, 0.86 for 12–23 months, and 1.11 for 24 months or longer. These results show the importance of

Moreover, Zheng et al. [38], in the period 1997–1999 in Shandong, China, studied breast cancer risk in 404 women and in a control group. Their results show that for those women who breastfed their children for more than 24 months, the odds ratio was 0.46 (95% CI, 0.27–0.78) when compared with those women who breastfed their child for 1–6 months. These data suggest that prolonged lactation reduces breast cancer risk. Similar results were found by Hajian-Tilaki et al. [39], in their study with 100 women diagnosed of breast cancer and 200 controls. The authors conclude that duration of breast feeding was inversely associated with breast cancer risk. In another case–control study in Tunisia between 2006 and 2009, involving 400 breast cancer cases and 400 controls, the authors likewise observed an inverse association

Other review study developed by Nagata et al. [41], in which they identified three cohort studies and five case–control studies show similar results as described above. There was no significant association between the risk of breast cancer and breastfeeding according cohort studies analyzed. Nevertheless, in most case–control studies observed a statistically significant reduction in risk for women who ever had breastfed or for women with longer breastfeeding duration. These results again suggest that breastfeeding decreases the risk of breast cancer

Despite the extensive scientific evidence available, there is still controversy about the effect of breastfeeding on the prevention of breast cancer. Consequently, more studies in different parts

Breastfeeding for periods of over 6 months results in statistically significant reductions in the risk of developing breast cancer, the most common gynecological tumor in young women. However, it remains to be studied further whether the observed risk reduction applies to women with inherited susceptibility to develop breast cancer. Further studies must be conducted to focus on populations in which breastfeeding was common for relatively long durations, and should attempt to collect information on the errors in the reporting of lifetime duration of breastfeeding and other forms of complementary feeding. Meanwhile, this

the breastfeeding duration in reducing the risk of breast cancer.

between breastfeeding duration and breast cancer risk [40].

of the world are needed to analyze this relationship [42].

populations are limited [35, 36].

among Japanese women.

5. Conclusions

#### 4. Breast milk

Breastfeeding is still another research focus. An increasing number of studies have indicated that breastfeeding offers protection against breast cancer [22, 23]. In the long term, the protection offered by breastfeeding is greater for premenopausal women, but also persists for postmenopausal women even after 50 years since the first lactation [24]. These protective effects of breastfeeding appear to be stronger the longer a woman breastfeeds her first child, as well as cumulative, such that increased lifetime duration of lactation over multiple children confers greater protection against breast cancer [25]. From a biological perspective, there are various explanations why breastfeeding seems to prevent breast cancer and why it appears to significantly benefit female health. One mechanism may involve a markedly reduced susceptibility of the fully differentiated mammary gland to carcinogens due to, at least in part, a decrease in proliferative activity of parous epithelium [26]. Other important changes are estrogen reduction and elimination through mammary fluid and the excretion of carcinogenic agents through the breast tissue during the breastfeeding process [27–29].

According to a study carried out by Cancer Research UK, the short duration of breastfeeding typical of women in developed countries makes a major contribution to the high incidence of breast cancer in these countries. The results obtained showed that the relative risk of breast cancer decreased by 7.0% for each birth in addition to a decrease of 4.3% for every 12 months of breastfeeding [30]. Despite such studies, many researchers are still skeptical as to the protection against breast cancer potentially afforded by breastfeeding. They claim that the data obtained until now are both insufficient and in many cases, inconsistent. Therefore, the influence of each birth should be considered when the relationship between breastfeeding and breast cancer is studied. Likewise, the reported breastfeeding duration is not very trusty, with values generally rounded to multiples of 6 or 12 months, particularly among women who had breastfed for long periods of time [31].

Nevertheless, a slightly lower rate of breast cancer was observed in women who breastfed their children for periods of over 12 months [32]. Of the women who had given birth, those who were cancer-free were more likely to have breastfed than those who subsequently developed breast cancer (79% as compared to 71%) [33]. However, a history of ever breast-feeding may be too crude an indicator, and it may be more important to demonstrate a dose–response association with increasing duration of breast-feeding in making causal inferences [34]. These results suggest an inverse relationship between breastfeeding duration and risk of developing breast cancer.

The decrease of relative risk´ rate of developing breast cancer associated with breastfeeding did not change significantly for women in developed and developing countries, and did not change according to the age and ethnicity [31]. Other studies have analyzed breast cancer risk factors, including breastfeeding duration, in Asian and African populations. The results obtained about breastfeeding duration and risk of developing breast cancer between these populations are limited [35, 36].

Additionally Michels et al. [37], in the Nurse's Health Study, in a retrospective review of breastfeeding duration in nearly 90,000 women, reported that, in comparison to never breastfeeding, the RR was 0.86 for fewer than 3 months of breastfeeding, 0.95 for 7–11 months, 0.86 for 12–23 months, and 1.11 for 24 months or longer. These results show the importance of the breastfeeding duration in reducing the risk of breast cancer.

Moreover, Zheng et al. [38], in the period 1997–1999 in Shandong, China, studied breast cancer risk in 404 women and in a control group. Their results show that for those women who breastfed their children for more than 24 months, the odds ratio was 0.46 (95% CI, 0.27–0.78) when compared with those women who breastfed their child for 1–6 months. These data suggest that prolonged lactation reduces breast cancer risk. Similar results were found by Hajian-Tilaki et al. [39], in their study with 100 women diagnosed of breast cancer and 200 controls. The authors conclude that duration of breast feeding was inversely associated with breast cancer risk. In another case–control study in Tunisia between 2006 and 2009, involving 400 breast cancer cases and 400 controls, the authors likewise observed an inverse association between breastfeeding duration and breast cancer risk [40].

Other review study developed by Nagata et al. [41], in which they identified three cohort studies and five case–control studies show similar results as described above. There was no significant association between the risk of breast cancer and breastfeeding according cohort studies analyzed. Nevertheless, in most case–control studies observed a statistically significant reduction in risk for women who ever had breastfed or for women with longer breastfeeding duration. These results again suggest that breastfeeding decreases the risk of breast cancer among Japanese women.

Despite the extensive scientific evidence available, there is still controversy about the effect of breastfeeding on the prevention of breast cancer. Consequently, more studies in different parts of the world are needed to analyze this relationship [42].
