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Journal of Peking University (Health Sciences) ›› 2022, Vol. 54 ›› Issue (5): 853-862. doi: 10.19723/j.issn.1671-167X.2022.05.013

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Clinicopathological features and prognosis of hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer

Yue WANG1,Shuang ZHANG1,Hong ZHANG1,Li LIANG1,Ling XU2,Yuan-jia CHENG2,Xue-ning DUAN2,Yin-hua LIU2,Ting LI1,*()   

  1. 1. Department of Pathology, Peking University First Hospital, Beijing 100034, China
    2. Breast Disease Center, Peking University First Hospital, Beijing 100034, China
  • Received:2022-06-22 Online:2022-10-18 Published:2022-10-14
  • Contact: Ting LI E-mail:lixiaoting12@hotmail.com
  • Supported by:
    the National Key R&D Program of China(2016YFC0901302)

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Abstract:

Objective: To investigate the clinicopathological features and prognosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2 -) breast cancer. Methods: In the study, 3 035 consecutive breast cancer patients diagnosed in Breast Disease Center, Peking University First Hospital from January 2008 to December 2017 were collected. The prognostic signi-ficance of important pathological factors in HR +/HER2 - patients with complete clinicopathological information was analyzed. Results: Within the 1 920 (63.26%) cases of HR +/HER2 - breast cancer, there were 1 624 cases with complete clinicopathological data, of which, 124 cases (7.64%) recurred and/or metastasized and 63 cases died of the disease, and the 5-year overall survival (OS) rate and disease-free survival (DFS) rate was 93.0% and 92.6% respectively. The stage of pT1-2 was 92.80%, while pN0 was 69.03%. 89.66% cases belonged to histologically non-specific type and 30.11%, 55.60%, 14.29% were credited to Grade 1, 2 and 3 respectively. The distribution of ER negative, low or high expression groups were 1.60%, 2.09% and 96.31%, while PR were 6.83%, 10.47%, 82.70%, respectively. The group of Ki67 index < 10% was 19.52%, ≥10% & < 20% for 32.02%, ≥20% for 48.46%. Survival analysis showed that cases with pT1 stage had lower risk of recurrence than those with pT3, while cases with pT2 and pT3 had shorter DFS than those with pT1, with higher risk of recurrence and metastasis. Analysis proved that both pN stage and histological grade were negatively correlated with DFS. The cases with pN0, pN1 and pN2 were lower risk of recurrence than those with pN3, while cases with Grade 1 and 2 had lower risk of recurrence than cases with Grade 3. And the group of Ki67 index ≥20% showed higher risk of recurrence and metastasis. The prognostic significance of ER expression in HR+/HER2- breast cancer was not significant. However, the negative/low PR expression groups showed higher risk of recurrence and metastasis, of which PR < 10% group had shortest DFS and OS, followed by 10%-60% group and then > 60% group. The most common site of metastasis was bone (55 cases, 44.35%), while cases with liver metastasis (30 cases, 24.20%) had the worst outcome. Conclusion: Our study revealed that pT, pN, Grade, HR expression level and Ki67 index were important prognostic factors for HR +/HER2 - breast cancer, although there are variables in prognostic value. Factors of pN and Grade showed independent prognostic significance. PR expression level had prognostic significance for the risk of recurrence and metastasis. The stratified level of PR expression (< 10%, 10%-60%, >60%) had independent prognostic value, showing successively longer DFS and OS, lower risk of recurrence. PR>60% group had the longest DFS and OS as well as the lowest risk of recurrence.

Key words: Breast neoplasms, Neoplasm recurrence, local, Neoplasm metastasis, Receptors, progesterone, Receptors, estrogen, Human epidermal growth factor receptor 2

CLC Number: 

  • R737.9

Table 1

Clinicopathological characteristics of 1 624 cases of HR +/HER2 - breast cancer patients"

Characteristics All cases (n=1 624) Metastasis (n=124) Non-metastasis (n=1 500)
Age/years 54 (21-92) 55 (22-90) 54 (21-92)
Gender
  Female 1 609 (99.08) 122 (98.39) 1 487 (99.13)
  Male 15 (0.92) 2 (1.61) 13 (0.87)
Family history
  Yes 57 (3.51) 3 (2.42) 54 (3.60)
  No 1 567 (96.49) 121 (97.58) 1 446 (96.40)
Menopausal statusa
  Premenopausal 562 (34.93) 41 (33.61) 521 (35.04)
  Postmenopausal 1 047 (65.07) 81 (66.39) 966 (64.96)
Surgery
  Breast-conserving surgery 460 (28.33) 26 (20.97) 434 (28.93)
  Mastectomy 1 164 (71.67) 98 (79.03) 1 066 (71.07)
Histologictype
  NOS 1 456 (89.66) 111 (89.52) 1 342 (89.47)
  ILC 69 (4.25) 9 (7.26) 60 (4.00)
  Mucinous carcinoma 69 (4.25) 0 69 (4.60)
  Othersb 30 (1.84) 4 (3.23) 29 (1.93)
pT stage
  1 913 (56.22) 54 (43.55) 859 (57.27)
  2 594 (36.58) 57 (45.97) 537 (35.80)
  3 117 (7.20) 13 (10.48) 104 (6.93)
pN stage
  0 1 121 (69.03) 51 (41.13) 1 070 (71.33)
  1 414 (25.49) 35 (28.23) 379 (25.27)
  2 52 (3.20) 17 (13.71) 35 (2.33)
  3 37 (2.28) 21 (16.93) 16 (1.07)
Grade
  1 489 (30.11) 24 (19.36) 465 (31.00)
  2 903 (55.60) 64 (51.61) 839 (55.93)
  3 232 (14.29) 36 (29.03) 196 (13.07)
ER
  ＜1% 26 (1.60) 3 (2.42) 23 (1.53)
  1%-10% 34 (2.09) 4 (3.23) 30 (2.00)
  >10% 1 564 (96.31) 117 (94.35) 1 447 (96.47)
PR
  ＜1% 111 (6.84) 11 (8.87) 100 (6.67)
  1%-10% 170 (10.47) 19 (15.32) 151 (10.07)
  11%-60% 301 (18.53) 33 (26.61) 268 (17.86)
  >60% 1 042 (64.16) 61 (49.19) 981 (65.40)
HR status
  ER+/PR+ 1 487 (91.57) 110 (88.71) 1 377 (91.80)
  ER+/PR- 111 (6.83) 11 (8.87) 100 (6.67)
  ER-/PR+ 26 (1.60) 3 (2.42) 23 (1.53)
HER2
  0 634 (39.04) 49 (39.52) 585 (39.00)
  1+ 612 (37.68) 44 (35.48) 568 (37.87)
  2+，FISH- 378 (23.28) 31 (25.00) 347 (23.13)
Ki67
  ＜10% 317 (19.52) 20 (16.13) 297 (19.80)
  ≥10%&<20% 520 (32.02) 24 (19.35) 496 (33.07)
  ≥20% 787 (48.46) 80 (64.52) 707 (47.13)
Molecular subtype
  Luminal A 516 (31.77) 44 (35.48) 472 (31.47)
  Luminal B 1 108 (68.23) 80 (64.52) 1 028 (68.53)
Endocrine therapyc
  No 11 (0.68) 3 (2.42) 8 (0.53)
  Preoperative 9 (0.55) 1 (0.81) 8 (0.53)
  Postoperative 1 609 (99.07) 120 (96.77) 1 489 (99.27)
Neoadjuvant chemotherapy
  No 1 392 (85.71) 93 (75.00) 1 299 (86.60)
  Yes 232 (14.29) 31 (25.00) 201 (13.40)
Adjuvant chemotherapy
  No 947 (58.31) 36 (29.03) 911 (60.73)
  Yes 677 (41.69) 88 (70.97) 589 (39.27)

Figure 1

Histopathological morphology of breast cancer and immunohistochemical staining of ER A, B, breast invasive carcinoma (NOS, ER was diffused strongly positive); C, D, invasive cribriform carcinoma of the breast (ER was diffused strongly positive); E, F, invasive apocrine carcinoma of the breast (5% ER positive expression); G, H, invasive micropapillary carcinoma of the breast (ER was diffused strongly positive). A, C, E, G, HE ×100; B, D, F, H, IHC ×100. Abbreviations as in Table 1."

Table 2

Univariate and multivariate analysis of clinicopathological features affecting tumor recurrence and metastasis of HR +/HER2 - breast cancer"

Variables Univariate Multivariate
HR (95%CI) P value HR (95%CI) P value
pT stage
  1 0.507 (0.276-0.928) 0.028 0.895
  2 0.822 (0.450-1.501) 0.523 0.850
  3 1.0 (reference)
pN stage
  0 0.070 (0.042-0.117) ＜0.001 0.081 (0.049-0.136) ＜0.001
  1 0.168 (0.098-0.289) ＜0.001 0.162 (0.093-0.280) ＜0.001
  2 0.427 (0.225-0.811) 0.009 0.472 (0.246-0.904) 0.024
  3 1.0 (reference) 1.0 (reference)
Grade
  1 0.258 (0.154-0.432) ＜0.001 0.327 (0.191-0.560) ＜0.001
  2 0.398 (0.265-0.599) ＜0.001 0.472 (0.311-0.717) ＜0.001
  3 1.0 (reference) 1.0 (reference)
ER
  ＜1% 1.069 (0.339-3.369) 0.909 0.795
  1%-10% 1.250 (0.461-3.390) 0.661 0.675
  >10% 1.0 (reference)
PR
  ＜10% 2.469 (1.592-3.830) ＜0.001 1.949 (1.247-3.047) 0.003
  10%-60% 1.970 (1.290-3.009) 0.002 1.724 (1.120-2.654) 0.013
  >60% 1.0 (reference) 1.0 (reference)
HER2
  0 0.793 (0.505-1.244) 0.313 0.530
  1+ 0.802 (0.506-1.270) 0.347 0.398
  2+，FISH- 1.0 (reference)
Ki67
  ＜10% 0.486 (0.298-0.795) 0.004 0.634
  ≥10%&<20% 0.435 (0.276-0.687) ＜0.001 0.341
  ≥20% 1.0 (reference)
Endocrine therapy
  No 0.242 (0.077-0.761) 0.015 3.221 (0.991-10.466) 0.052
  Yes 1.0 (reference) 1.0 (reference)
Neoadjuvant chemotherapy
  No 0.620 (0.412-0.932) 0.022 0.214
  Yes 1.0 (reference)

Figure 2

Estimates of DFS and OS in HR +/HER2 - breast cancer patients with different groups by Kaplan-Meier survival analysis with Log-rank test A, pT staging; B, pN staging; C, histological grading; D, ER (cutoff value were 1% and 10%); E, PR (cutoff value were 1% and 10%); F, PR reclassification (cutoff value were 10% and 60%); G, ER (cutoff value were 10% and 60%), DFS; H, ER (cutoff value were 10% and 60%), OS; I, HR; J, Ki67; K, first metastatic site. DFS, disease-free survival; OS, overall survival. Other abbreviations as in Table 1."

Figure 3

Distribution of HR and Ki67 in 1 624 cases of HR +/HER2 - breast cancer Abbreviations as in Table 1."

Figure 4

Time-dependent ROC of ER (A) and PR (B) expression level A, time-dependent ROC of ER expression level suggested that ER had no predictive value for survival; B, time-dependent ROC of PR expression level showed that the AUC of area under 5-year survival curve was 0.687 and that of area under 3-year survival curve was 0.665."

Figure 5

Cluster analysis of HR distribution and important clinicopathological parameters HR, hormone receptor. pN 0/1/2/3 were assigned with 0/1/2/3; Non-metastasis/metastasis were assigned with 0/1; Ki67 < 10%, ≥10%&<20%, ≥20% were assigned with 0, 1, 2 respectively; Grade 1/2/3 were assigned with 0/1/2; Luminal A/B were assigned with 0/1."

Table 3

Correlation between HR expression status and clinicopathological characteristics of patients with HR +/HER2 - breast cancer"

Variables HR+/HER2- breast cancer HR+/HER2- breast cancer with relapse
ER+/PR+
(n=1 487)		 ER+/PR-
(n=111)		 ER-/PR+
(n=26)		 P ER+/PR+
(n=110)		 ER+/PR-
(n=11)		 ER-/PR+
(n=3)		 P
Menopausal statusa ＜0.001 0.038
  Premenopausal 531 (36.05) 17 (15.45) 14 (53.85) 36 (33.33) 2 (18.18) 3 (100.00)
  Postmenopausal 942 (63.95) 93 (84.55) 12 (46.15) 72 (66.67) 9 (81.82) 0
pT stage 0.555 0.993
  1 836 (56.22) 60 (54.05) 17 (65.38) 49 (44.54) 4 (36.36) 1 (33.33)
  2 543 (36.52) 43 (38.74) 8 (30.77) 48 (43.64) 7 (63.64) 2 (66.67)
  3 108 (7.26) 8 (7.21) 1 (3.85) 13 (11.82) 0 0
pN stage 0.042 0.781
  0 1 036 (69.67) 65 (58.56) 20 (76.92) 45 (40.91) 4 (36.36) 2 (66.67)
  1-3 451 (30.33) 46 (41.44) 6 (23.08) 65 (59.09) 7 (63.64) 1 (33.33)
Grade ＜0.001 0.948
  1 457 (30.73) 28 (25.23) 4 (15.38) 22 (20.00) 2 (18.18) 0
  2 840 (56.49) 54 (48.65) 9 (34.62) 55 (50.00) 6 (54.55) 3 (100.00)
  3 190 (12.78) 29 (26.12) 13 (50.00) 33 (30.00) 3 (27.27) 0
Ki67 ＜0.001 0.669
  ＜10% 303 (20.38) 10 (9.01) 4 (15.38) 19 (17.27) 0 1 (33.33)
  ≥10%&<20% 487 (32.75) 33 (29.73) 0 21 (19.09) 3 (27.27) 0
  ≥20% 697 (46.87) 68 (61.26) 22 (84.62) 70 (63.64) 8 (72.73) 2 (66.67)
Molecular subtype ＜0.001 0.016
  Luminal A 501 (33.69) 11 (9.91) 4 (15.38) 43 (39.09) 0 1 (33.33)
  Luminal B 986 (66.31) 100 (90.09) 22 (84.62) 67 (60.91) 11 (100.00) 2 (66.67)

Figure 6

Ki67 index among different HR expression status HR, hormone receptor; ER, estrogen receptor; PR, progesterone receptor."

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