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. 2018 Apr 19;7(6):2753–2763. doi: 10.1002/cam4.1503

Comparison of epidemiological features, clinicopathological features, and treatments between premenopausal and postmenopausal female breast cancer patients in western China: a retrospective multicenter study of 15,389 female patients

Fan Feng 1,†, Yuxian Wei 1, Ke Zheng 1, Yujing Li 2, Lu Zhang 1, Tielin Wang 1, Yanli Zhang 1, Hongyuan Li 1, Guosheng Ren 1, Fan Li 1,✉
PMCID: PMC6010855  PMID: 29673111

Abstract

Premenopausal and postmenopausal breast cancers are considered different types. Thus, this study aimed to explore differences in risk factors, epidemiological features, clinicopathological features, and treatment modes of premenopausal breast cancer compared to postmenopausal patients in western China. This was a hospital‐based, retrospective, multicenter epidemiological study of patients with breast cancer. Using the Western China Clinical Cooperation Group database, we obtained the records of 15,389 female breast cancers between January 2010 and April 2017. These patients were divided into premenopausal and postmenopausal groups, and their risk factors, epidemiological feature, clinicopathological features, and treatment modes were compared. Chi‐square tests, t‐test, and the multivariate logistic regression analysis were applied for statistical analysis. A total of 8395 patients were categorized as premenopausal, and 6994 patients were categorized as postmenopausal. Their risk factors, epidemiological features, clinicopathological features, and treatment modes were compared. Premenopausal patients with breast cancer had a greater tumor diameter at diagnosis (P = 0.008); higher rates of estrogen receptor (ER) expression (P < 0.0001), progesterone receptor (PR) expression (P < 0.0001), negative human epidermal growth factor receptor 2 (HER2) expression (P = 0.015), and negative P53 expression (P < 0.0001); and higher proportions of receiving breast‐conserving surgery and breast reconstruction (P < 0.0001), chemotherapy (P < 0.0001), radiotherapy (P < 0.0001), and endocrine therapy (P < 0.0001). The ethnicity, age at menarche, marital status, number of pregnancies, and number of births were the risk factors for age at diagnosis of breast cancer before or after menopause in western China. We found that the fall in the fertility rate, early menarche age, married, and less breastfeeding might have increased the possibility of premenopausal breast cancer. Significant differences exist in the tumor size, hormone receptor state, HER2 expression, epidemiological features, and treatment modes between premenopausal and postmenopausal female breast cancer patients in western China. Its further implementation requires prospective clinical testing.

Keywords: Breast cancer, hormone receptor, postmenopausal, pregnancy, premenopausal

Introduction

Breast cancer is the most common cancer in women, and its incidence is increasing annually worldwide 1, 2. Breast cancer is also a heterogeneous disease, divisible into various clinical subtypes, and the pathogenesis is not clear 3. As early as the 1970s, De Waard proposed the concept that breast cancers develop by two distinct pathways, each with a different age‐specific incidence rate curve 4, 5. The first pathway results in mainly premenopausal tumors with peak occurrence early in life. The second pathway results in predominantly postmenopausal cancers with peak incidence later in life, similar to late‐onset estrogen receptor(ER)‐positive cancers.

In China, the data from both Shanghai and Beijing showed two breast cancer age peaks, one at 45–55 years and the other at 70–74 years 6. The mean age at diagnosis of breast cancer in China is 45–55 years, which is considerably younger than that for western women, with 57.4% of women diagnosed before the age of 50 years and 62.9% of women diagnosed while still premenopausal; the peak incidence occurred after menopause in developed countries 7. This result suggests the possibility that certain differences in the pathogenesis of breast cancer may exist between Chinese women and women in Western populations.

Few studies have investigated the risk factors that may influence the age at diagnosis of breast cancer. The difference in the clinicopathologic features and treatment modes between premenopausal and postmenopausal patients with breast cancer is not known. Some scholars have predicted that the incidence of hormone receptor‐positive breast cancer is affected by the menopause transition 8, 9. Nonetheless, and somewhat paradoxically, it has been reported that menopause significantly affects the incidence of ER‐negative breast cancer but not that of ER‐positive breast cancer 10, 11. Presently, this issue is controversial.

Currently, no study has compared the difference between premenopausal and postmenopausal breast cancers in China. Therefore, the main objective of this study was to assess the epidemiological characteristics, clinicopathologic features, and treatment modes between premenopausal and postmenopausal breast cancers to make treatment decisions and improve patient prognoses, as well as to provide valuable insights into what may influence the age at diagnosis of breast cancer in western China.

Materials and Methods

Study design

The Western China Clinical Cooperation Group (WCCCG) was established in 2008 and includes 23 breast cancer centers in nine provinces in western China. A total of 18,000 patients with breast cancer are included in the database. Male patients and female patients without menopausal status and age at diagnosis were excluded from the study. In total, 15,389 patients with breast cancer who were diagnosed between 1 January 2009 and 30 April 2017 were included in the retrospective multicenter database analysis. Among them, 8395 patients (54.55%) were divided into premenopausal group, and 6994 patients (45.45%) were divided into postmenopausal group. This observational study was based entirely on data extracted from patient medical records and was approved by the ethics committee of each participating center.

Patients

The data for this study, including demographic data and tumor data, were extracted from the medical records of the patients included herein by trained data collectors at each center and were analyzed anonymously.

Data collection

Demographic data included information regarding the age at diagnosis, race, age at menarche, marital status, and number of pregnancies, number of births, breastfeeding history, and body mass index. Clinical characteristics consisted of tumor laterality, location in the breast, axillary and supraclavicular lymph node status, and size in cm. The tumors were classified according to initial disease symptoms and signs and whether there was distant metastasis in the body. The following pathologic characteristics were evaluated in the study: tumor histological types, axillary lymph node metastases, numbers of positive axillary lymph nodes, the presence of lymph vascular invasion, tumor grade, ER and PR status, HER2 and P53 expression, and Ki67 status. Data regarding treatments were also collected and included the chemotherapy regimens, radiotherapy regimens, anti‐HER2 therapy regimens, endocrine therapy regimens, types of surgeries, and axillary lymph node dissection procedures.

Pathological grading and staging criteria

The tumor was graded according to the Bloom–Richardson classification (Nottingham grading) 12. Staging of breast cancer size was performed according to the American Joint Committee on Cancer (AJCC) TNM staging system (from 1997 and 2002) 13. All centers use the same criteria.

Statistical analyses

Statistical analyses were performed using the Statistical Package for the Social Sciences, version 22.0 (SPSS Inc., Chicago, IL, USA). The differences in the demographic, clinical, and pathological characteristics and in treatments between the two groups were analyzed using Student's t‐test in the case of quantitative variables and chi‐square tests and Fisher's exact test in the case of categorical variables. Multivariate logistic regression analyses were performed to assess the associations between menopausal status and several variables, and odds ratios (ORs) were calculated based on 95% confidence intervals. Variables with univariate results of P < 0.05 were included in the multivariate model. All statistical tests were considered significant when P < 0.05.

Results

Comparison of the baseline characteristics

The comparison of the baseline characteristics of premenopausal and postmenopausal groups is summarized in Table 1. The mean ages at diagnosis of the patients in premenopausal and postmenopausal groups were 42.8 and 58.2 years, respectively, and there was a difference in the distributions of the ages at which patients were diagnosed between the two groups (P < 0.0001). The proportion of patients of Han ethnicity was lower in premenopausal group than in postmenopausal group (94.69% vs. 96.61%, respectively, P < 0.0001). Most of the patients in the two groups experienced menarche at 13–14 years [n = 4396 (52.36%) and n = 3456 (49.41%), respectively]. Patients in premenopausal group were younger at the time of menarche (younger than 12 years) than patients in postmenopausal group. In addition, more patients in postmenopausal group experienced menarche at an age older than 15 years (P < 0.0001).We also observed differences in the marital status (P < 0.0001), number of pregnancies (P < 0.0001), number of births (P = 0.002), and breastfeeding history (P < 0.0001) between the two groups. The mean body mass indexes (BMI) of the patients in premenopausal and postmenopausal groups were 23.1 and 23.6, respectively. An analysis of BMI showed that premenopausal group included more patients who had a BMI <25.0 compared with that postmenopausal group [n = 3693 (43.99%) and n = 2825 (40.39%), respectively] (P < 0.0001).

Table 1.

Baseline characteristics of the patients with breast cancer

Characteristics Total (N = 15,389) Premenopausal (N = 8395) Postmenopausal (N = 6994) P value
N % N % N %
Age
Mean ± SD 49.6 ± 11.1 42.8 ± 7.0 58.2 ± 8.5 <0.0001a
Race/ethnicity
Han 14,706 95.51 7949 94.69 6757 96.61 <0.0001b
Other 683 4.44 446 5.31 237 3.39
Age at menarche (years)
≤10 30 0.19 20 0.24 10 0.14 <0.0001b
11–12 1844 11.98 1191 14.19 653 9.34
13–14 7852 50.99 4396 52.36 3456 49.41
15–16 3981 25.85 2089 24.88 1892 27.05
17–18 1349 8.76 583 6.94 766 10.95
≥19 284 1.84 98 1.17 186 2.66
Missing data 49 0.32 18 0.21 31 0.44
Marital status
Married 14,960 97.16 8188 97.53 6772 96.83 <0.0001c
Never married 138 0.90 110 1.31 28 0.40
Widowed/divorced 276 1.79 89 1.06 187 2.67
Missing data 15 0.10 8 0.10 7 0.10
Number of pregnancies
0 3239 21.04 1790 21.32 1449 20.72 <0.0001b
1 3848 24.99 2216 26.40 1632 23.33
2 3228 20.96 1807 21.52 1421 20.32
3 2228 14.47 1230 14.65 998 14.27
4 1408 9.14 715 8.52 693 9.91
≥5 1413 9.18 623 7.42 790 11.30
Missing data 25 0.16 14 0.17 11 0.16
Number of births
0 2753 17.88 1584 18.87 1169 16.71 <0.0001b
1 7086 46.02 4404 52.46 2682 38.35
2 3579 23.24 1887 22.48 1692 24.19
3 1198 7.78 378 4.50 820 11.72
4 468 3.04 97 1.16 371 5.30
≥5 282 1.83 32 0.38 250 3.57
Missing data 23 0.15 13 0.15 10 0.14
Breastfeeding history
No 1543 10.02 900 10.72 643 9.19 0.002b
Yes 5050 32.80 2685 31.98 2365 33.81
Missing data 8796 57.12 4810 57.30 3986 56.99
BMI <0.0001a
Mean ± SD 23.3 ± 2.5 23.1 ± 2.4 23.6 ± 2.7 <0.0001b
<18.5 442 2.87 252 3.00 190 2.72
18.5~24.9 6076 39.46 3441 40.99 2635 37.68
25.0~29.9 2184 14.18 983 11.71 1201 17.17
≥30.0 308 2.00 129 1.54 179 2.56
Missing data 6379 41.43 3590 42.76 2789 39.88
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a

Student's t‐test.

b

Chi‐square test.

c

Fisher's exact test.

Comparison of clinical characteristics

Table 2 shows significant differences in the occurrence of breast pain (8.33% vs. 9.75%, P = 0.002), nipple discharge (2.30% vs. 2.83%, P = 0.037), and nipple inversion (1.21% vs. 2.04%, P < 0.0001). Patients in postmenopausal group were more likely to have a positive axillary lymph node status (29.40% vs. 27.95%, P = 0.031) and supraclavicular lymph node status (5.85% vs. 4.93%, P = 0.007). However, no significant difference in the incidence of distant metastases was observed between the two groups (1.70% vs. 2.10%, P = 0.073). Regarding the tumor size, most patients in the two groups had a tumor size between 2 and 5 cm, whereas significantly more patients in premenopausal group had large tumors (8.1% vs. 7.55%, P = 0.008).

Table 2.

Clinical characteristics of the tumors

Characteristics Total (N = 15,389) Premenopausal (N = 8395) Postmenopausal (N = 6994) P value
N % N % N %
Breast lump
Yes 14,485 94.07 7913 94.26 6572 93.97 0.482a
No 904 5.87 483 5.75 421 6.02
Breast pain
Yes 1381 8.97 699 8.33 682 9.75 0.002a
No 14,008 90.97 7697 91.69 6311 90.23
Nipple discharge
Yes 391 2.54 193 2.30 198 2.83 0.037a
No 14,998 97.40 8203 97.71 6795 97.15
Nipple inversion
Yes 254 1.65 111 1.32 143 2.04 <0.0001a
No 15,135 98.29 8285 98.69 6850 97.94
Tumor location in breast
3 o'clock 385 2.50 214 2.55 171 2.44 <0.0001a
6 o'clock 259 1.68 138 1.64 121 1.73
9 o'clock 475 3.08 254 3.03 221 3.16
12 o'clock 813 5.28 478 5.69 335 4.79
Upper inner quadrant 1975 12.83 1190 14.18 785 11.22
Lower inner quadrant 577 3.75 326 3.88 251 3.59
Upper outer quadrant 5637 36.61 3238 38.57 2399 34.30
Lower outer quadrant 1119 7.27 624 7.43 495 7.08
Nipple–areola 910 5.91 449 5.35 461 6.59
Missing data 3239 21.04 1484 17.68 1755 25.09
Axillary lymph lode status
Positive 4402 28.59 2346 27.95 2056 29.40 0.031b
Negative 10,097 65.57 5578 66.44 4519 64.61
Missing data 890 5.78 471 5.61 419 5.99
Supraclavicular lymph lode status
Positive 823 5.34 414 4.93 409 5.85 0.007b
Negative 13,557 88.04 7480 89.10 6077 86.89
Missing data 1009 6.55 501 5.97 508 7.26
Tumor size (cm)
≤1 820 5.33 485 5.78 335 4.79 0.008a
>1,≤2 4456 28.94 2370 28.23 2086 29.83
>2,≤5 7158 46.49 3907 46.54 3251 46.48
>5 1208 7.85 680 8.10 528 7.55
Missing data 1747 11.35 953 11.35 794 11.35
Distant metastasis
Positive 290 1.88 143 1.70 147 2.10 0.073a
Negative 14,951 97.10 8165 97.26 6786 97.03
Missing data 148 0.96 87 1.04 61 0.87
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a

Chi‐square test.

b

Fisher's exact test.

Comparison of pathological characteristics

Pathological characteristics are displayed in Table 3. Regarding ER, PR, human epidermal growth factor receptor‐2 (HER‐2), P53 status and Ki67, with which the patients receiving immunohistochemistry testing presented, we found that patients in premenopausal group were more likely to show positive expression of ER (59.14% vs. 54.86%, P < 0.0001) and PR (55.76% vs. 43.78%, P < 0.0001) than postmenopausal group. Premenopausal patients also had higher proportions of double‐positive expression of ER and PR (i.e., ER+/PR+; 50.46% vs. 40.43%, P < 0.0001) and single‐positive expression of PR (i.e., ER−/PR+; 5.28% vs. 3.33%, P < 0.0001). Conversely, patients in postmenopausal group presented with double‐negative expression of ER and PR (i.e., ER−/PR−; 35.72% vs. 31.40%, P < 0.0001) and single‐positive expression of ER (i.e., ER+/PR−; 14.20% vs. 8.29%, P < 0.0001) more frequently. Moreover, the proportion of patients with a positive HER2 status (14.46% vs. 13.48%, P = 0.015) and P53 status (29.47% vs. 25.63%, P < 0.0001) was higher in postmenopausal group. However, no significant difference in the incidence of triple‐negative or Ki67 was observed between the two groups.

Table 3.

Pathological characteristics of the tumors

Characteristics Total (N = 15,389) Premenopausal (N = 8395) Postmenopausal (N = 6994) P value
N % N % N %
Tumor histology
Carcinoma in situ 801 5.20 413 4.92 388 5.55 0.053a
Invasive carcinoma 14,008 90.97 7712 91.86 6296 90.02
Missing data 580 3.77 270 3.22 310 4.43
Axillary lymph nodes metastasis
Yes 6584 42.76 3612 43.03 2972 42.49 0.914a
No 7210 46.82 3962 47.19 3248 46.44
Missing data 1595 10.36 821 9.78 774 11.07
No. of positive axillary lymph nodes
0 (N0) 7210 46.82 3962 47.19 3248 46.44 0.068a
1–3 (N1) 4125 26.79 2285 27.22 1840 26.31
4–9 (N2) 1572 10.21 877 10.45 695 9.94
≥10 (N3) 887 5.76 450 5.36 437 6.25
Missing data 1595 10.36 821 9.78 774 11.07
Lymphovascular invasion
Yes 270 1.75 155 1.85 115 1.64 0.099a
No 6873 44.64 3594 42.81 3279 46.88
Missing data 8246 53.55 4646 55.34 3600 51.47
Tumor grade
I 554 3.60 292 3.48 262 3.75 0.588a
II 5384 34.97 2776 33.07 2608 37.29
III 1893 12.29 1002 11.94 891 12.74
Uncertain 1546 10.04 785 9.35 761 10.88
Missing data 5988 38.89 3527 42.01 2461 35.19
ER+/PR+
Yes 7269 50.46 4236 40.43 2828 41.25 <0.0001a
No 7324 45.21 3795 53.35 3731 52.56
Missing data 796 4.34 364 6.22 435 6.19
ER+/PR−
Yes 1722 8.29 696 14.20 993 14.41 <0.0001a
No 12,871 87.21 7321 79.40 5553 79.40
Missing data 796 4.50 378 6.41 448 6.19
ER−/PR+
Yes 1722 5.28 443 3.33 233 14.41 <0.0001a
No 12,871 90.22 7574 90.26 6313 79.40
Missing data 796 4.50 378 6.41 448 6.19
ER−/PR−
Yes 4916 31.40 2636 35.72 2498 34.69 <0.0001a
No 9677 64.26 5395 58.06 4061 59.12
Missing data 796 4.34 364 6.22 435 6.19
HER2 status
Yes 2143 13.92 1132 13.48 1011 14.46 0.015a
No 8063 52.36 4496 53.56 3567 51.00
Uncertain 2475 16.07 1257 14.97 1218 17.41
Missing data 2708 17.59 1510 17.99 1198 17.13
Triple‐negative
Yes 2372 15.40 1279 15.24 1093 15.63 0.502a
No 13,017 84.54 7116 84.76 5901 84.37
P53 status
Yes 4213 27.36 2152 25.63 2061 29.47 <0.0001a
No 2304 14.96 1060 12.63 1244 17.79
Missing data 8872 57.62 5183 61.74 3689 52.75
Ki67
≥14 4772 30.99 2534 30.18 2238 32.00 0.715a
14 2712 17.61 1452 17.30 1260 18.02
Missing data 7905 51.34 4409 52.52 3496 49.99
ER status
Yes 8802 59.14 4965 54.86 3837 29.47 <0.0001a
No 5816 36.70 3081 39.10 2735 17.79
Missing data 771 4.16 349 6.03 422 52.75
PR status
Yes 4772 55.76 4681 43.78 3062 32.00 <0.0001a
No 2712 39.93 3352 50.03 3499 18.02
Missing data 7905 4.31 362 6.19 433 49.99
Open in a new tab
a

Chi‐square test.

Comparison of treatment modes

We found that most patients received chemotherapy and that patients in premenopausal group received chemotherapy (85.06% vs. 75.72%, P < 0.0001), radiotherapy (20.31% vs. 13.14%, P < 0.0001), and endocrine therapy (29.77% vs. 22.79%, P < 0.0001) more frequently. Of the 15,389 patients included in the study, 14,521 patients underwent surgery. Patients in premenopausal group were more likely to undergo breast‐conserving surgery, simple mastectomy, and breast reconstruction and were less likely to undergo modified radical mastectomy than patients in postmenopausal group (P < 0.0001). The comparison of the treatment characteristics between the two groups is presented in Table 4.

Table 4.

Treatments of the patients with breast cancer

Characteristics Total (N = 15,389) Premenopausal (N = 8395) Postmenopausal (N = 6994) P value
N % N % N %
Chemotherapy
Yes 12,437 80.77 7141 85.06 5296 75.72 <0.0001a
No 2294 14.90 960 11.44 1334 19.07
Missing data 668 4.34 294 3.50 374 5.35
Radiotherapy
Yes 2624 17.04 1705 20.31 919 13.14 <0.0001a
No 12,058 78.31 6373 75.91 5685 81.28
Missing data 707 4.59 317 3.78 390 5.58
Anti‐HER2 therapy
Yes 136 0.88 75 0.89 61 0.87 0.978a
No 14,571 94.63 8018 95.51 6553 93.69
Missing data 682 4.43 302 3.60 380 5.43
Endocrine therapy
Yes 4093 26.58 2499 29.77 1594 22.79 <0.0001a
No 10,584 68.74 5574 66.40 5010 71.63
Missing data 712 4.62 322 3.84 390 5.58
Type of surgery
Modified radical mastectomy 11,467 74.47 6061 72.20 5406 77.29 <0.0001a
Breast‐conserving surgery 1582 10.27 986 11.75 596 8.52
Simple mastectomy 793 5.15 451 5.37 342 4.89
Radical mastectomy 196 1.27 115 1.37 81 1.16
Extensive radical mastectomy 103 0.67 58 0.69 45 0.64
Breast reconstruction 380 2.47 314 3.74 66 0.94
Missing data 868 5.64 410 4.88 458 6.55
Axillary lymph node dissection
Yes 13,065 84.85 7145 85.11 5920 84.64 0.058a
No 1575 10.23 901 10.73 674 9.64
Missing data 749 4.86 349 4.16 400 5.72
Level of axillary lymph node dissection
Level I, II 9504 61.72 5220 62.18 4284 61.25 0.485a
Level III 1867 12.12 1009 12.02 858 12.27
Missing data 4018 26.09 2166 25.80 1852 26.48
Open in a new tab
a

Chi‐square test.

Multivariate logistic regression analysis of premenopausal breast cancer‐related risk factors among all breast cancer patients

Multivariate logistic regression analysis indicated following risk factors were related to premenopausal breast cancer: ethnicity, age at menarche, marital status, number of pregnancies, and number of births. Compared with referent (Han; age at menarche ≤10; married; absence of a history of pregnancy and birth): (1) other ethnicities and number of pregnancy ≥1 were associated with elevated premenopausal breast cancer possibility (OR > 1, P < 0.05); (2) and increase in age at menarche, never married, widowed/divorced, and number of birth ≥1 were associated with decreased premenopausal breast cancer possibility (OR<1, P < 0.05) among all breast cancer patients. All the results of multivariate logistic regression analysis are listed in Table 5.

Table 5.

Multivariate logistic regression analysis of premenopausal breast cancer‐related risk factors

Factors B Sb χ 2 P value OR (95% CI)
Ethnicity
Hana
Other 0.87 0.091 91.048 <0.001 2.388 (1.997–2.855)
Age at menarche
≤10a
11–12 −1.038 0.413 6.33 0.012 0.354 (0.158–0.795)
13–14 −1.013 0.141 51.852 <0.001 0.363 (0.276–0.479)
15–16 −0.71 0.133 28.356 <0.001 0.492 (0.378–0.638)
17–18 −0.6 0.135 19.673 <0.001 0.549 (0.421–0.716)
≥19 −0.295 0.143 4.243 0.039 0.745 (0.563–0.986)
Marital status
Marrieda
Never married −0.88 0.138 40.648 <0.001 0.415 (0.317–0.544)
Widowed/ divorced −1.832 0.256 51.151 <0.001 0.16 (0.097–0.264)
Number of pregnancies
0a
1 0.49 0.095 26.637 <0.001 1.632 (1.355–1.965)
2 0.668 0.081 67.892 <0.001 1.95 (1.664–2.286)
3 0.359 0.078 21.342 <0.001 1.432 (1.229–1.667)
Number of births
0a
1 −2.895 0.214 183.38 <0.001 0.055 (0.036–0.084)
2 −3.071 0.205 225.333 <0.001 0.046 (0.031–0.069)
3 −2.496 0.204 149.986 <0.001 0.082 (0.055–0.123)
4 −1.48 0.208 50.452 <0.001 0.228 (0.151–0.343)
≥5 −0.835 0.228 13.392 <0.001 0.434 (0.278–0.679)
Open in a new tab
a

Referent.

Discussion

Overall, it is of great interest that a significant difference exists between premenopausal and postmenopausal female breast cancer patients and we found some factors that are associated with elevated or decreased premenopausal breast cancer possibility. The related research is rare.

Consistent with the results of other scholars in China 6, 14, the median age at diagnosis was 49.6 years for all breast cancer patients in this study. The premenopausal patients accounted for 54.55% of the total breast cancer cases, the proportion was significantly higher than that of postmenopausal patients, and that differed from the corresponding proportion in a Western population 15. This finding suggests the possibility that certain differences in the pathogenesis of breast cancer, considered to be related to ethnicity, age at menarche, marital status, number of pregnancies, number of births, and breastfeeding history 16, 17, 18, 19, may exist between premenopausal and postmenopausal patients.

The onset of the premenopausal peak is considered related to a birth cohort effect, resulting from changes in the menstrual and reproductive patterns and other lifestyle changes 20, 21. Further research results in our study supported this possibility. First, multivariate logistic regression analysis indicated that other ethnicities and number of pregnancy ≥1 were associated with elevated premenopausal breast cancer possibility (OR > 1, P < 0.05). We found a significantly higher proportion of the minority nationalities and times of pregnancy ≥1 in premenopausal women. It was reported that the incidence age of breast cancer of minority nationalities was earlier than that of the Han nationality 22. Second, multivariate logistic regression analysis showed that increase in age at menarche, never married, widowed/divorced, and number of birth ≥1 were associated with decreased premenopausal breast cancer possibility (OR < 1, P < 0.05). We found that the age of postmenopausal women experienced menarche was older than that of premenopausal women in this study. Previous studies have suggested that early age at menarche is a risk factor leading to the advanced onset of breast cancer 16, 23, 24. We also noted that a higher proportion of postmenopausal women had more than two births and a history of breastfeeding. A meta‐analysis of 47 studies in 30 countries showed that breastfeeding could reduce the risk of breast cancer 25. Bao concluded that increased numbers of births per woman were associated with a reduced risk of breast cancer for postmenopausal women 17. We found the number of pregnancies was positively associated with risk of premenopausal breast cancer, but increased number of births decreased the risk of that. Because of the one‐child policy and some other reasons, Chinese women may not to give a birth after pregnancy. Here come to a conclusion that only pregnancy but no childbirth might increase the risk of premenopausal breast cancer. We speculate that the fall in the fertility rate 26, 27, early menarche age, the married and less breastfeeding might have increased the possibility of premenopausal breast cancer.

A Westernized lifestyle, particularly an increase in the obesity prevalence and physical inactivity in recent decades, is likely to affect the observed rise in breast cancer incidence 28, 29. Obesity was considered a mechanism of breast cancer in postmenopausal women 30. These results guide postmenopausal women to adjust their diet, strengthen exercises, and reduce the risk factors of breast cancer that can be controlled artificially.

Breast cancer is age‐dependent, and it is widely accepted that young women tend to present with a greater tumor size that is more advanced and with poorer prognostic characteristics 31, 32. We found that premenopausal women presented with a greater tumor size (more than 2 cm) than postmenopausal women in our study. The fact might imply there are also more aggressive breast cancers in Chinese premenopausal patients than in postmenopausal.

We further analyzed the difference in the pathological features between the two groups. The ER and PR status are important indicators to guide endocrine therapy in breast cancer. It is also an important factor affecting the prognosis of breast cancer 33, 34. Wittliff studied the relationship between menopausal status and ER and reported that the positive expression of ER occurred at a rate of 45% in premenopausal women and at a rate of <63% in postmenopausal patients 35. Anderson reported that ER‐positive rates rose continuously irrespective of menopause 36. However, we found the opposite. That is, the positive expression of ER occurred at a rate of 59% in premenopausal women and was higher than 55% in postmenopausal patients. We also found that postmenopausal patients had higher proportions of positive HER2 expression and positive P53 expression. Scholars have reported a negative correlation between the positive expression of ER and positive HER2 status 37, 38. We obtained similar results. Those results are similar to that in another article from the same database 32. Additionally, higher proportion of (ER+/PR+) in premenopausal patients and higher proportion of (ER−/PR−) in postmenopausal patients suggested that the distribution of hormone receptors in western Chinese women is different from that in foreign countries. The reasons for the difference in the expression of hormone receptor may be as follows: (1) the proportion of premenopausal and postmenopausal women with breast cancer in China is opposite of that in foreign countries 15; (2) the stimulation of different human populations and the external environment affect the expression of hormone receptor; and (3) pregnancy and childbirth lead to the fluctuation of estrogen and progesterone levels, which affect the expression of hormone receptor. The relationship between menopause and ER and PR remains controversial, and we need more large‐scale studies to clarify their relationship.

Regarding treatment options, we compared the following five aspects between the two groups: surgery, chemotherapy, radiotherapy, endocrine therapy, and anti‐HER2 therapy. First, we found that 94% of all patients underwent surgery. Regarding the choice of surgical approach, a higher proportion of premenopausal patients underwent advanced operation methods, such as breast‐conserving surgery and breast reconstruction. A possible explanation was that younger patients have a greater desire to keep their original breasts and shapes and are more accepting of advanced operation methods compared to postmenopausal patients 39. Second, we found that there are more premenopausal patients receiving chemotherapy. Chemotherapy is one of the most commonly used and most effective methods among adjuvant therapies for treating breast cancer. Premenopausal patients had a smaller average age, higher malignancy, and risk of recurrence of the tumors 32, and it was reported that chemotherapy can significantly reduce the risk of relapse of high malignant breast cancer 34, 40, so they could benefit more from chemotherapy. The discovery of more aggressive cancers found in premenopausal women is the fact that leads to more chemotherapy in this population. Third, we found that a higher proportion of premenopausal patients receiving radiotherapy, as radiotherapy is necessary after breast‐conserving surgery, and that the proportion of premenopausal patients receiving breast‐conserving surgery were higher. Additionally, adjuvant radiotherapy after surgery significantly reduces the local recurrence rate and increases the overall survival rate 41. Similarly, the proportion of premenopausal patients receiving endocrine therapy was significantly higher than that of postmenopausal patients. The increased use of endocrine therapy may be due to the fact that endocrine therapy is suitable for hormone receptor‐positive breast cancer and significantly reduces the recurrence rate 42, and the proportion of (ER+/PR+) in premenopausal patients was significantly higher. Finally, this study showed that very few patients with a positive HER2 status accepted anti‐HER2 therapy. The possible reason may be that the HER2 testing condition is deficient in local areas. Additionally, anti‐HER2 therapy is not included in health care, indicating that it is a costly burden in western China.

Limitations

Our study had some limitations. First, all patients included were from nine provinces of western China; thus, the results may not be generalizable to all women in China. Second, data regarding some characteristics, such as HER2 status, BMI, breastfeeding history, tumor location, P53 status, and Ki67 status, were missing, which may have underpowered the study. Another limitation is that we failed to follow up the patients. As a result, we cannot analyze the relationship between prognosis and clinicopathologic features.

Conclusion

In this study, we found that the fall in the fertility rate, early menarche age, married, and less breastfeeding might have increased the possibility of premenopausal breast cancer. Significant differences exist in the tumor size, hormone receptor state, HER2 expression, epidemiological features, and treatment modes between premenopausal and postmenopausal female breast cancer patients in western China. The difference in breast cancer onset period remains to be investigated in the further studies.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Conflict of Interest

The authors have no disclosures.

Acknowledgments

We thank Professor Ren for providing access to the Western China Clinical Cooperation Group database.

Cancer Medicine 2018; 7(6):2753–2763

References

  • 1. Siegel, R. L. , Miller K. D., Fedewa S. A., Ahnen D. J., Meester R. G., Barzi A., et al. 2017. Colorectal cancer statistics, 2017. CA Cancer J. Clin. 67:177–193. [DOI] [PubMed] [Google Scholar]
  • 2. Chen, W. , Zheng R., Baade P. D., Zhang S., Zeng H., Bray F., et al. 2016. Cancer statistics in China, 2015. CA Cancer J. Clin. 66:115–132. [DOI] [PubMed] [Google Scholar]
  • 3. Anderson, W. F. , Rosenberg P. S., Prat A., Perou C. M., and Sherman M. E.. 2014. How many etiological subtypes of breast cancer: two, three, four, or more? J. Natl Cancer Inst. 106:296–297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4. De, W. F. , Baanders‐Vanhalewijn E. A., and Huizinga J.. 1964. The bimodal age distribution of patients with mammary carcinoma; evidence for the existence of 2 types of human breast cancer. Cancer 17:141–151. [DOI] [PubMed] [Google Scholar]
  • 5. Waard, F. D. 1979. Premenopausal and postmenopausal breast cancer: one disease or two? J. Natl Cancer Inst. 63:549–552. [DOI] [PubMed] [Google Scholar]
  • 6. Fan, L. , Zheng Y., Yu K. D., Liu G. Y., Wu J., Lu J. S., et al. 2009. Breast cancer in a transitional society over 18 years: trends and present status in Shanghai, China. Breast Cancer Res. Treat. 117:409–416. [DOI] [PubMed] [Google Scholar]
  • 7. Fan, L. , Strasser‐Weippl K., Li J. J., St Louis J., Finkelstein D. M., Yu K. D., et al. 2014. Breast cancer in China. Lancet Oncol. 15:e279–e289. [DOI] [PubMed] [Google Scholar]
  • 8. Yasui, Y. , and Potter J. D.. 1999. The shape of age‐incidence curves of female breast cancer by hormone‐receptor status. Cancer Causes Control 10:431–437. [DOI] [PubMed] [Google Scholar]
  • 9. Tarone, R. E. , and Chu K. C.. 2002. The greater impact of menopause on ER− than ER+ breast cancer incidence: a possible explanation (United States). Cancer Causes Control 13:7–14. [DOI] [PubMed] [Google Scholar]
  • 10. Morabia, A. , and Costanza M. C.. 1998. International variability in ages at menarche, first livebirth, and menopause. Am. J. Epidemiol. 148:1195–1205. [DOI] [PubMed] [Google Scholar]
  • 11. Morabia, A. , and Flandre P.. 1992. Misclassification bias related to definition of menopausal status in case‐control studies of breast cancer. Int. J. Epidemiol. 21:222–228. [DOI] [PubMed] [Google Scholar]
  • 12. Elston, C. W. , and Ellis I. O.. 1991. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up. Histopathology 19:403–410. [DOI] [PubMed] [Google Scholar]
  • 13. Singletary, S. E. , and Connolly J. L.. 2006. Breast cancer staging: working with the sixth edition of the AJCC Cancer Staging Manual. CA Cancer J. Clin. 56:37–47. [DOI] [PubMed] [Google Scholar]
  • 14. Li, J. , Zhang B. N., Fan J. H., Pang Y., Zhang P., Wang S. L., et al. 2011. A nation‐wide multicenter 10‐year (1999–2008) retrospective clinical epidemiological study of female breast cancer in China. BMC Cancer 11:364. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Althuis, M. D. , Dozier J. M., Anderson W. F., Devesa S. S., and Brinton L. A.. 2005. Global trends in breast cancer incidence and mortality 1973–1997. Int. J. Epidemiol. 34:405–412. [DOI] [PubMed] [Google Scholar]
  • 16. Gao, Y. T. , Shu X. O., Dai Q., Potter J. D., Brinton L. A., Wen W., et al. 2000. Association of menstrual and reproductive factors with breast cancer risk: results from the Shanghai breast cancer study. Int. J. Epidemiol. 87:295–300. [DOI] [PubMed] [Google Scholar]
  • 17. Bao, P. P. , Shu X. O., Gao Y. T., Zheng Y., Cai H., Deming S. L., et al. 2011. Association of hormone‐related characteristics and breast cancer risk by estrogen receptor/progesterone receptor status in the Shanghai breast cancer study. Am. J. Epidemiol. 174:661–671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. Ali, P. , Fakhree M. B. A., Shahryar H., Monireh H., and Amir D.. 2011. Hormone receptor status in breast cancer and its relation to age and other prognostic factors. Breast Cancer 5:87–92. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. Lin, C. H. , Chuang P. Y., Chiang C. J., Lu Y. S., Cheng A. L., Kuo W. H., et al. 2014. Distinct clinicopathological features and prognosis of emerging young‐female breast cancer in an East Asian country: a nationwide cancer registry‐based study. Oncologist. 19:583–591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20. Linos, E. , Spanos D., Rosner B. A., Linos K., Hesketh T., Qu J. D., et al. 2008. Effects of reproductive and demographic changes on breast cancer incidence in China: a modeling analysis. J. Natl Cancer Inst. 100:1352–1360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21. Wong, I. O. , Cowling B. J., Schooling C. M., and Leung G. M.. 2007. Age‐period‐cohort projections of breast cancer incidence in a rapidly transitioning Chinese population. Int. J. Cancer 121:1556–1563. [DOI] [PubMed] [Google Scholar]
  • 22. Ademuyiwa, F. O. , and Olopade O. I.. 2003. Racial differences in genetic factors associated with breast cancer. Cancer Metastasis Rev. 22:47–53. [DOI] [PubMed] [Google Scholar]
  • 23. Byrne, C. , Connolly J. L., Colditz G. A., and Schnitt S. J.. 2015. Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk. Cancer 89:2046–2052. [DOI] [PubMed] [Google Scholar]
  • 24. Chen, W. Y. , Hankinson S. E., Schnitt S. J., Rosner B. A., Holmes M. D., and Colditz G. A.. 2004. Association of hormone replacement therapy to estrogen and progesterone receptor status in invasive breast carcinoma. Cancer 101:1490–1500. [DOI] [PubMed] [Google Scholar]
  • 25. Hamajima, N. , Hirose K., Tajima K., Rohan T., Calle E. E., Jr H. C., et al. 2002. Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58 515 women with breast cancer and 95 067 women without the disease. Br. J. Cancer 87:1234–1245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26. http://www.wpro.who.int/topics/adolescent_health/china_fs.pdf, 2014.
  • 27. Li, L. , Ji J., Wang J. B., Niyazi M., Qiao Y. L., and Boffetta P.. 2012. Attributable causes of breast cancer and ovarian cancer in China: reproductive factors, oral contraceptives and hormone replacement therapy. Chin. J. Cancer Res. 24:9–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. Goss, P. E. , Strasser‐Weippl K., Lee‐Bychkovsky B. L., Fan L., Li J., Chavarri‐Guerra Y., et al. 2014. Challenges to effective cancer control in China, India, and Russia. Lancet Oncol. 15:489–538. [DOI] [PubMed] [Google Scholar]
  • 29. Varghese, C. , and Shin H. R.. 2014. Strengthening cancer control in China. Lancet Oncol. 15:484–485. [DOI] [PubMed] [Google Scholar]
  • 30. Renehan, A. G. , Tyson M., Egger M., Heller R. F., and Zwahlen M.. 2008. Body‐mass index and incidence of cancer: a systematic review and meta‐analysis of prospective observational studies. Lancet 371:569–578. [DOI] [PubMed] [Google Scholar]
  • 31. Anders, C. K. , Hsu D. S., Broadwater G., Acharya C. R., Foekens J. A., Zhang Y., et al. 2008. Young age at diagnosis correlates with worse prognosis and defines a subset of breast cancers with shared patterns of gene expression. J. Clin. Oncol. 26:3324–3330. [DOI] [PubMed] [Google Scholar]
  • 32. Ke, W. , Yu R., Li H., Ke Z., Jiang J., Zou T., et al. 2016. Comparison of clinicopathological features and treatments between young (≤40 years) and older (>40 years) female breast cancer patients in west China: a retrospective, epidemiological, multicenter, case only study. PLoS ONE 11:e0152312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33. Gao, J. D. , Wang J., Feng X. L., Zhong Y. X., and Wang X.. 2009. Characterization of hormone receptor status in 5758 Chinese females with breast cancer. Chin. J. Oncol. 31:683–686. [PubMed] [Google Scholar]
  • 34. Early Breast Cancer Trialists’ Collaborative Group . 2005. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15‐year survival: an overview of the randomised trials. Lancet 365:1687–1717. [DOI] [PubMed] [Google Scholar]
  • 35. Wittliff, J. L. 1984. Steroid‐Hormone receptors in breast cancer. Cancer 53:630–643. [DOI] [PubMed] [Google Scholar]
  • 36. Anderson, W. F. , Rosenberg P. S., Menashe I., Mitani A., and Pfeiffer R. M.. 2008. Age‐related crossover in breast cancer incidence rates between black and white ethnic groups. J. Natl Cancer Inst. 100:1804–1814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Lamy, P. J. , Verjat T., Paye M., Servanton A. C., Grenier J., Leissner P., et al. 2006. NASBA: a novel approach to assess hormonal receptors and ERBB2 status in breast cancer. Clin. Chem. Lab. Med. 44:3–12. [DOI] [PubMed] [Google Scholar]
  • 38. Lee, A. , Park W. C., Yim H. W., Lee M. A., Park G., and Lee K. Y.. 2007. Expression of c‐erbB2, cyclin D1 and estrogen receptor and their clinical implications in the invasive ductal carcinoma of the breast. Jpn. J. Clin. Oncol. 37:708–714. [DOI] [PubMed] [Google Scholar]
  • 39. Huang, N. , Liu M., Chen J., Yang B., Xue J., C. Quan , et al. 2016. Surgical management of breast cancer in China: a 15‐year single‐center retrospective study of 18502 patients. Medicine 95:e4201. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40. Early Breast Cancer Trialists’ Collaborative Group . 1998. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet 352:930–942. [PubMed] [Google Scholar]
  • 41. Clarke, M. , Collins R., Darby S., Davies C., Elphinstone P., Evans V., et al. 2007. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15‐year survival: an overview of the randomised trials. Lancet 366:2087–2106. [DOI] [PubMed] [Google Scholar]
  • 42. Hackshaw, A. , Baum M., Fornander T., Nordenskjold B., Nicolucci A., Monson K., et al. 2009. Long‐term effectiveness of adjuvant goserelin in premenopausal women with early breast cancer. J. Natl Cancer Inst. 101:341–349. [DOI] [PMC free article] [PubMed] [Google Scholar]

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