Breast J. 2019;00:1–5. wileyonlinelibrary.com/journal/tbj © 2019 Wiley Periodicals, Inc. | 1
Received: 3 July 2019
|
Revised: 30 July 2019|
Accepted: 1 August 2019 DOI: 10.1111/tbj.13520S H O R T C O M M U N I C A T I O N
A retrospective study on breast cancer presentation, risk
factors, and protective factors in patients with a positive family history of breast cancer
Ying Yi Liaw MBBS
1| Foong Shiang Loong MBBS
1| Suzanne Tan MBBS
1| Sze Yun On MBBS
1| Evelyn Khaw MBBS
1| Yilynn Chiew MBBS
1| Rusli Nordin MBBS, PhD
1| Tuan Nur Mat MBBS, MS
2| Sarojah Arulanantham MBBS, MS
3| Anil Gandhi MBBS, MS
11Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Bandar Sunway, Malaysia
2Head of Department (Surgery), Hospital Sultanah Aminah (HSA), Johor Bahru, Malaysia
3Head of Department (Surgery), Hospital Sultan Ismail (HSI), Johor Bahru, Malaysia Correspondence
Anil Gandhi, Clinical School Johor Bahru, Monash University Malaysia, 8, Masjid Sultan Abu Bakar, 80100, Johor Bahru, Malaysia.
Email: [email protected]
Abstract
Women with a positive family history of breast cancer are greatly predisposed to breast cancer development. From January 2007 to December 2016, 1101 patients with a histologically confirmed breast cancer were divided into two groups: patients with and without a positive family history of breast cancer. Variables including age at presentation, ethnicity, tumor size, age at menarche, age at menopause, oral contra‐
ceptive pill (OCP) use, hormone replacement therapy (HRT), alcohol intake, smoking, body mass index (BMI), diabetes mellitus, parity, and breastfeeding were recorded.
One hundred and fifty‐nine out of 1101 (14.4%) of the patients had a family history of breast cancer. There was no significant difference in the incidence of breast cancer among Malays, Chinese, and Indians. Both patient groups presented at a mean age of about 60 years (+FH 60; ‐FH 61.2 P‐value = .218). Significantly higher prevalence of history of benign breast disease (11.3%, P .018), nulliparity (13.2%, P .014), tumor size at presentation of more than 5 cm (47.3%, P 0.001), and bilateral site presenta‐
tion (3.1%, P 0.029) were noted among respondents with a positive family history of breast cancer compared to those with a negative family history of breast cancer.
The odds of having a tumor size larger than 5cm at presentation were almost two times higher in patients with a positive family history as compared to those without a family history (adjusted OR = 1.786, 95% CI 1.211‐2.484) (P‐value .003). Women in Malaysia, despite having a positive family history of breast cancer, still present late at a mean age of 60 with a large tumor size of more than 5 cm, reflecting a lack of aware‐
ness. Breastfeeding does not protect women with a family history from developing breast cancer.
K E Y W O R D S
breast cancer, clinical presentation, family history, Malaysian women, risk factors
1 | INTRODUCTION
Breast cancer remains a significant cause of morbidity and mortal‐
ity among women globally, notwithstanding Malaysia.1 As reported by the Malaysian National Cancer Registry Report in 2016, women in Malaysia have a lifetime risk of 1 in 9 for cancer.2 Breast cancer, the most common cancer among Malaysian women, accounts up to 31.1% of all cancer cases.2 Furthermore, the overall 5‐year survival rate of female patients with breast cancer in Malaysia appeared to be low in comparison with the developed nations.3
This study focuses on women with a positive family history of breast cancer because these women are known to have a twofold increase in breast cancer risk, as compared to those without a family history.4 The aim of this study was to determine the effect of a pos‐
itive family history on breast cancer presentation. Additionally, this study investigates the degree of influence of both risk and protec‐
tive factors of breast cancer among these high‐risk women.
2 | METHODS
The study was conducted in two large tertiary hospitals in Johor Bahru. Ethical clearance was obtained from the Medical Research and Ethics Committee (MREC) and from each of the hospitals’ Clinical Research Centre. All women above the age of 18 with a histologically confirmed breast cancer, from January 2007 to December 2016, were eligible for the study.
Subjects of the study were divided into two groups: breast can‐
cer patients with at least one relative with breast cancer and breast cancer patients with no family history. Variables including age at presentation, ethnicity, tumor size, tumor unilaterality (unilateral or bilateral), age at menarche, age at menopause, oral contraceptive pill (OCP) use, hormone replacement therapy (HRT) use, alcohol intake, smoking, BMI, diabetes mellitus, parity, and breastfeeding were re‐
corded using a standardized data collection sheet.
3 | STATISTICAL ANALYSIS
Data were checked for normality using the stem and leaf plot, and the Kolmogorov‐Smirnov test. Mean and standard deviations were computed for continuous variables; frequencies and percentages for categorical variables; corresponding 95% confidence intervals (CIs) were computed where necessary. To determine the asso‐
ciation between sociodemographic and comorbid variables and family history of breast cancer, the chi‐square tests (Pearson's chi‐square test, Fisher's exact test, and Mantel‐Haenszel test for trend) were computed and statistical significance was set at P < .05. Multicollinearity and outliers were checked before under‐
taking the logistic regression analyses. Univariate binary logistic regression was undertaken to determine significant predictors in patients with family history of breast cancer. All significant pre‐
dictors (P < .25) were included in the multivariate binary logistic
regression using the stepwise method. Significant (P < .05) and in‐
dependent predictors in the family history of breast cancer were included in the final model.
4 | RESULTS
A total of 1101 women diagnosed with breast cancer confirmed by histopathology examination were reviewed. 159 out of all patients (14.4%) had at least one family member with breast cancer. There was no significant difference in the incidence of positive family his‐
tory between Malays, Chinese, and Indians. Additionally, both pa‐
tient groups, with or without a positive family history, presented at a mean age of 60.
Significantly higher prevalence of tumor size at presentation of more than 5 cm (47.3%, P = .001), nulliparity (13.2%, P = .014), history of benign breast disease (11.3%, P = .018), and bilateral site presentation (3.1%, P = .029) was noted among respondents with a positive family history of breast cancer compared to those with a negative family history of breast cancer (P < .05; Table 1).
The univariate analyses of the factors surrounding breast can‐
cer in relation to family history were shown in Table 1. There were significant differences between patients with a family history and patients without a family history in terms of tumor size (P = .001) and tumor site (unilateral vs bilateral) (P = .029) at presentation. There were no significant differences between the two patient groups in terms of age at menarche, OCP use, HRT use, alcohol intake, smok‐
ing, BMI, diabetes mellitus, and breastfeeding.
Significant predictors of breast cancer in those with a positive family history of breast cancer, shown in Table 2, were past history of other cancers (adjusted OR = 4.053; 95%CI:1.102‐14.901) and tumor size at presentation (adjusted OR = 1.734; 95%CI:1.211‐2.484).
Parity of two or more was marginally significant (P = .057) and pro‐
tective (P = .540) of a positive family history of breast cancer (ad‐
justed OR = 0.583, 95%CI:0.334‐1.016).
Table 3 demonstrated the results of multivariate analyses, of which only tumor size was found to be statistically significant (P‐
value = .001). The odds of having a tumor size larger than 5 cm at presentation were almost two times higher in patients with a pos‐
itive family history as compared to those without a family history (adjusted OR = 1.786, 95%:CI 1.251‐2.549).
5 | DISCUSSION
A positive family history of breast cancer is known to signifi‐
cantly increase the risk of a woman developing breast cancer.4,5 This study revealed an incidence of a positive family history of 14.4% in patients with breast cancer. A local study done by Cheng et al reported a similar result, with 16.2% of their patients with breast cancer having at least one relative with breast cancer.6 Furthermore, the study showed no association between ethnicity and incidence of a positive family history of breast cancer among
TA B L E 1 Sociodemographic characteristics of the study population (N = 1101) Sociodemographic characteristic
Negative family history of Breast cancer no. (%)
Positive family history of breast
cancer no. (%) P‐value
Age (y) mean (SD) 60.0 (7.66) 61.2 (7.95) .218a
Age at menarche (year) mean (SD) 13.2 (1.14) 13.0 (1.08) .179a
Age of menopause (y) mean (SD) 50.7 (2.95) 51.0 (3.28) .395a
BMI (kg/m2) mean (SD) 26.5 (4.29) 26.0 (3.35) .293a
Race
Malay 536 (56.9) 102 (64.2) .319b
Chinese 280 (29.7) 39 (24.5)
Indian 113 (12.0) 15 ( 9.4)
Other 13 ( 1.4) 3 ( 1.9)
History of benign breast disease
No 884 (93.8) 141 (88.7) .018b
Yes 58 ( 6.2) 18 (11.3)
Past history of other cancer
No 933 (99.0) 155 (97.5) .105c
Yes 9 ( 1.0) 4 ( 2.5)
Parity
0 80 ( 8.5) 21 (13.2) .014b
1 73 ( 7.7) 20 (12.6)
>1 789 (83.8) 118 (74.2)
Age at first childbirth (year) mean (SD)
<30 199 (81.2) 36 (75.0) .322b
30 and older 46 (18.8) 12 (25.0)
Breastfeeding
No 130 (31.9) 27 (35.5) .540b
Yes 277 (68.1) 49 (64.5)
OCP
No 297 (59.9) 56 (60.2) .952b
Yes 199 (40.1) 37 (39.8)
HRT
No 160 (88.4) 21 (84.0) .516c
Yes 21 (11.6) 4 (16.0)
Alcohol intake
No 255 (95.9) 70 (94.6) .748c
Yes 11 ( 4.1) 4 ( 5.4)
Smoking
No 288 (96.3) 79 (96.3) 1.000c
Yes 11 ( 3.7) 3 ( 3.7)
Diabetes
No 717 (76.8) 120 (75.9) .805b
Yes 216 (23.2) 38 (24.1)
Tumor size at presentation (cm)
<5 548 (66.5) 77 (52.7) .001b
>5 276 (33.5) 69 (47.3)
Site
Unilateral 929 (99.1) 154 (96.9) .029c
Bilateral 8 ( 0.9) 5 ( 3.1)
aIndependent t test.
bPearson's chi‐square test.
cFisher's exact test.
Malaysia multiethnic population.6 Such finding was similarly dem‐
onstrated in this study.
In relation to the age of presentation, breast cancer patients with a positive family history were found to present at a younger age of <40, as compared to those without a positive family history.6 Nevertheless, the opposite was observed in this study. Patients with breast cancer in this study presented late at an average age of 61.2, despite having a positive family history. This finding reflected a low level of awareness among Malaysian women and an inadequate sur‐
veillance for these high‐risk women.
The low level of awareness was also evident upon further evalu‐
ation of the tumor size at presentation among breast cancer patients with and without a family history. Studies done in Western countries observed not only a younger age of presentation but also a smaller tumor size of about 2 cm, in women with a known family history of breast cancer.7 In this study, breast cancer patients with a positive family history had a higher tendency of presenting with a large tumor size of more than 5cm, as compared to those without a family history.
Similarly, in the local study done by Cheng HY et al, Malaysian women presented with a large tumor size of 4cm despite having a positive family history.6 This may be because of lack of awareness among Malaysia population which could be a result of poor understanding of disease, different sociocultural beliefs, personal fear, strong belief in complementary medicine, and geographical barriers.8
Furthermore, this study observed no significant difference between women with and without a family history in term of
frequencies of unilateral and bilateral breast cancer. This finding was similarly reported by Tazzite et al9 On the contrary, Magid reported a greater tendency of patients with a family history to develop bilat‐
eral breast cancer particularly of the metachronous type.10 In gen‐
eral, an early age of menarche was known to increase the risk of breast cancer.11 However, upon investigating the impact of the age at menarche in relation to family history, there was no significant association observed in this study. This finding was further substan‐
tiated by the meta‐analyses of other studies, which revealed similar effects of age of menarche among women, regardless of the pres‐
ence of family history of breast cancer.12
The use of OCP was also shown to have minimal effect as a risk factor in women with a positive family history. A pooled meta‐anal‐
ysis of 52 studies reported a 2.5 times greater risk of developing breast cancer in women with one or more first‐degree relatives with breast cancer and have consumed OCP.12
In addition, HRT is a known risk factor for breast cancer.13 Shah et al reported a 39% increase in the risk of breast cancer with postmenopausal combined estrogen and progesterone hor‐
mone therapy with OR = 1.35 (95%CI:1.16‐1.57) and OR = 1.63 (95%CI:1.22‐2.18) for less than and more than 5 years of use, re‐
spectively.13 However, HRT use in women with a positive family history of breast cancer was not associated with a greater inci‐
dence of breast cancer.14 The noninteracting effect of family history and HRT on the incidence of breast cancer was similarly demonstrated in this study also.
Despite the strong association between alcohol consumption and breast cancer,15 alcohol use had no additive effect on the risk of breast cancer among women with a family history.16 This study observed similar result. To be exact, there was no difference in the effect of smoking on breast cancer risk among women with and without a family history. This result was consistent with other stud‐
ies which reported no interaction between family history and smok‐
ing.17 In fact, Reynolds et al reported a strong smoking‐associated risk among women without a family history but not among women with a family history.18
BMI has no significant effect on the risk of breast cancer during the premenopausal period but overweight and obesity during the postmenopausal period are associated with a slight increase in risk.11 Such associations remained similar when comparing women with and without a family history in our study, revealing a consistent result with that reported by Magnusson C et al19 Diabetes mellitus poses a higher risk for breast cancer.20 The presence of family history in individuals with diabetes mellitus further increased the risk of breast cancer from a relative risk of 1.36 to 1.87 (95%CI:0.93‐3.76).21 This association was not demonstrated in this study.
Parous women are known to have a lower risk of developing breast cancer.11 Based on 13 meta‐analysis studies, the risk for breast cancer was significantly decreased in women with 3 or more births compared with nulliparous women (RR = 0.73, 95%CI:0.61‐0.87).11 Another study established that parity entails similar association with breast cancer risk among women with and without a family history, as reported by Magnusson C et al19 In this study, parity of TA B L E 2 Predictors of family history of breast cancer: stepwise
multiple logistic regression analysis
Characteristics Adjusted OR
95% CI for ad‐
justed OR
P‐value Lower Upper
Past history of other cancer
Yes 1 1.10 14.90 .035
No 4.05
Parity
0 1
1 1.06 0.51 2.21 .871
≥1 0.58 0.33 1.02 .057
Tumor size at presentation
≤5 cm 1
≥5 cm 1.73 1.21 2.48 .003
Bold to show significance of P < .05.
TA B L E 3 Multivariate analyses of tumor size and laterality associated with breast cancer in relation to family history
Characteristics Adjusted. OR 95% CI P‐value Tumor size (>5 cm) 1.786 1.25‐2.55 .001 Tumor site
(bilateral)
2.436 0.72‐8.30 .155
Bold to show significance of P < .05.
two or more was marginally significant (P = .057) and protective (B = −0.540) of a positive family history of breast cancer (adjusted OR = 0.583, 95%CI:0.334, 1.016).
Moreover, it was reported in a systematic review of 69 studies that breastfeeding lowered the risk of breast cancer by approx‐
imately 11%.22 This finding was supported by another meta‐anal‐
ysis whereby women who breastfeed were shown to have a 13%
decreased risk for breast cancer.11 The greater reduction in risk for breast cancer with increasing duration of breastfeeding was re‐
ported by Claude et al and Alison et al among women with a pos‐
itive family history of breast cancer. Nonetheless, this finding was not evident in this study.23,24 The contradicting findings indicate an information gap that would require further investigation by conduct‐
ing more studies.
6 | CONCLUSION
Malaysian women, despite having a positive family history, pre‐
sented late at an average age of 60 years with a large tumor size of more than 5 cm. This finding reflected a low level of awareness which signified the need for more public education and informa‐
tional campaigns. Additionally, parity of two or more was marginally significant and protective of a positive family history of breast can‐
cer. Furthermore, breastfeeding was observed to have no protective effect on women with a positive family history. Regular mammo‐
graphic breast screening could be the only means for early detection of breast cancer among these high‐risk women.
ORCID
Anil Gandhi https://orcid.org/0000‐0001‐6721‐5880
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How to cite this article: Liaw YY, Loong FS, Tan S, et al.
A retrospective study on breast cancer presentation, risk factors, and protective factors in patients with a positive family history of breast cancer. Breast J. 2019;00:1–5.
https ://doi.org/10.1111/tbj.13520
