Breast cancer in Chinese elderly women: Pathological and clinical characteristics and factors influencing treatment patterns

Critical Reviews in Oncology/Hematology 71 (2009) 258–265

Breast cancer in Chinese elderly women: Pathological and clinical characteristics and factors influencing treatment patterns Chuan-Dong Ma a , Qin Zhou b , Xiu-Qing Nie a , Guang-Yu Liu a , Gen-Hong Di a , Jiong Wu a , Jin-Song Lu a , Wen-Tao Yang c , Jia-Yi Chen d , Zhi-Min Shao a , Kun-Wei Shen a , Zhen-Zhou Shen a,∗ a

Department of Breast Surgery, Cancer Hospital, Fudan University, 270 Dong’An Road, Shanghai 200032, PR China b Department of Health Statistics, School of Public Health, Fudan University, Shanghai, PR China c Department of Pathology, Cancer Hospital, Fudan University, Shanghai, PR China d Department of Radiation Oncology, Cancer Hospital, Fudan University, Shanghai, PR China Accepted 21 November 2008

Contents 1. 2. 3.

4.

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Patients and methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Statistical methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1. Pathological characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2. Biological characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3. Comorbid illness . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4. Local and systemic treatments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5. Multinomial and binary logistic regression . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflicts of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Reviewers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Biographies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

259 259 259 260 260 260 260 261 261 262 264 264 264 265

Abstract The aims of this study are to describe tumor characteristics and treatment patterns of elder breast cancer patients and to determine the factors influencing local and systemic treatments. This retrospective cohort included 866 patients (≥60 years) referred for surgery between January 2002 and December 2006. The patients were divided into four groups according to age. Elderly women had larger tumors at diagnosis with more mucinous carcinomas, more estrogen/progesterone-positive, lower Ki-67 labeling indices and less c-erbB2 positive tumors. Comorbidities were more often recorded for older patients. They were more likely to undergo simple mastectomy or breast-conserving surgery, less likely to receive adjuvant chemotherapy and radiotherapy, compared with their younger counterparts. Multinomial and binary logistic regression showed that age was independently associated with local and systemic treatments. Our data suggest that the tumors of elderly patients are biologically more favorable, and elderly women appear to receive less aggressive treatments. © 2008 Elsevier Ireland Ltd. All rights reserved. Keywords: Breast cancer; Elderly patients; Biological/pathological/clinical characteristics; Treatment ∗

Corresponding author. Tel.: +86 21 64175590; fax: +86 21 64173822. E-mail address: [email protected] (Z.-Z. Shen).

1040-8428/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.critrevonc.2008.11.005

C.-D. Ma et al. / Critical Reviews in Oncology/Hematology 71 (2009) 258–265

1. Introduction Breast cancer is a common malignant disease among women throughout the world, and in recent years breast carcinoma is emerging as the commonest female malignancy in the developing Asian countries [1]. In China, the leading cancer in terms of incidence in the year 2005 was breast cancer for women [2]. As the population ages, it is expected that the magnitude of elderly patients with breast carcinoma will increase. In the United States, the population 65 years or older accounted for 11.3% of the total population in 1980, and is estimated to reach 20.1% by 2030 [3]. Approximately 50% of breast cancers occur in women aged ≥65 years, and >30% of breast cancers occur among women aged >70 years [4]. Although the magnitude of elderly patients with breast carcinoma increased, low percentages of patients aged >70 years are represented in randomized clinical trials [5,6]. Recent recommendations of the International Society for Geriatric Oncology have been published [7], but because of the widely held belief that the tumor of elderly patients is a more indolent disease, elderly patients with breast cancer often receive a pattern of less intensive care [7–13]. The choice of adjuvant treatment for elderly patients should be based on the same criteria that are currently used for patients in other age groups: endocrine responsiveness and assessment of risk of relapse [7,14]. However, additional factors should be considered in treatment decisions, including life expectancy, comorbid conditions, benefits and possible toxicity of treatments, functional status, cognitive status, economic and social support, and the viewpoints of both the physician and the patient [7,15,16]. The clinical and pathological characteristics and treatment patterns of elderly women with breast cancer in the developed countries has been well documented [5,8,17,18]. However, information on tumor features and patterns of care for older patients from the developing countries is relatively scarce. In addition, the clinical and pathological attributes of this disease in Asian women are different from the rest of the world [1]. In this study, we reviewed the clinical, biological and pathological characteristics and treatment patterns of women age ≥60 years with early breast cancer at a large institution in recent 5 years. The aim of this study was to compare tumor characteristics and treatment modalities of elder patients with those of younger postmenopausal patients, and to determine the factors influencing local and systemic adjuvant treatment decisions.

259

eral carcinoma or recurrent breast cancer were excluded, and Women with locally advanced breast cancer who underwent neoadjuvant chemotherapy or primary hormonal therapy were also excluded. Data for the pathological and biological characteristics of tumors were extracted from clinical charts, the following data were also gathered: age, other comorbid medical conditions, surgery, radiation, and systemic treatment (hormonal therapy or chemotherapy). When necessary, systemic treatment details of patients were attained by telephone interview. Estrogen receptor (ER) level, progesterone receptor (PgR) level, P53 status, C-erbB-2 status, and Ki-67 labeling index were evaluated immunohistochemically. Hormonal receptor was positive if either estrogen receptor or progesterone receptor was more than 10 fmol/mg or more than 10% of the cells were stained. The extent of staining for p53 protein was graded semiquantitatively using a “–” through 3+ scale, with “–” representing no staining at all, 1+ representing <25% staining, 2+ representing 25–75% staining, and 3+ representing >75% staining of the tumor cells present in the sections [19]. C-erbB-2 protein staining results was scored on a scale of “–” to 3+: uniform intense membrane staining of >10% of invasive tumor cells was defined as 3+, weak to moderate complete membrane staining in at least 10% of tumor cells was 2+, incomplete membrane staining in any proportion of tumor cells was 1+, no staining or weak was “–”. FISH testing of Her2 gene amplification was not routinely performed in our institute. The cutoff value for Ki-67 labeling index was 30% as previously reported [5]. Histological grade was evaluated according to Elston and Ellis grading, and peritumoral vascular invasion was assessed according to Rosen and Oberman [20]. Rather than using Charlson’s scale [21], we simply classified comorbid conditions as absent or present. In terms of surgical therapy, we defined the type of surgery: modified radical mastectomy (MRM), radical mastectomy (RM), mastectomy (simple mastectomy), breast-conserving surgery (wide resection or quadrantectomy, with axillary dissection or not, BCS). Adjuvant cytotoxic regimens in this study mainly including: CMF (cyclophosphamide, methotrexate and 5-fluorouracil), anthracycline-based regimens such as AC (doxorubicin and cyclophosphamide), CAF (cyclophosphamide, doxorubicin and 5-fluorouracil), CEF (cyclophosphamide, epirubicin and 5-fluorouracil), and capecitabine alone. Endocrine treatments were mainly tamoxifen and aromatase inhibitors (AIs) such as letrozole, anatrozole. 2.1. Statistical methods

2. Patients and methods This retrospective cohort involved 866 early breast cancer patents age ≥60 years who underwent surgery at Fudan University affiliated Cancer Hospital between January 2002 and December 2006. Women with ductal carcinoma in situ, bilat-

We compared tumor characteristics, multidisciplinary treatments among four groups of patients: 60–64 years, 65–69 years, 70–74 years and ≥75 years. The associations between categorical variables and age groups were examined in contingency table using chi-square test or Fisher’s exact test. Binary and multinomial logistic regression analyses were

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C.-D. Ma et al. / Critical Reviews in Oncology/Hematology 71 (2009) 258–265

performed to estimate the interdependence of tumor characteristics, biologic features, and age on treatment. The final model contained the variables that were significant at the 5% level. Interaction tests were used to investigate the homogeneity of effects over the four age groups. In all analyses, a two-sided P-value <0.05 was considered significant. All statistics were performed using SPSS software (SPSS 11.5 for Windows, SPSS Inc., Chicago, IL).

at diagnosis than younger women (P < 0.01). Lymph node involvement was not significantly different among four age groups (P > 0.05). There were statistically significant differences in histology based on age, with women aged ≥75 years having more mucinous carcinomas and other histological subtypes (P > 0.001). In the case of tumor grade and peritumoral vascular invasion, there was no statistically significant difference among the four age groups (P > 0.05).

3. Results

3.2. Biological characteristics

A total of 4821 primary invasive breast cancer patients were referred for surgery in our hospital between January 2002 and December 2006, 910 patients were ≥60 years old. Eight patients presenting with bilateral carcinoma were excluded from the study, and 36 patients presenting with locally advanced breast cancer at diagnosis were also excluded. Of the remaining 866 patients, 293 patients were classified as 60–64 years group, 250 patients as 65–69 years group, 161 patients as 70–74 years group, and 162 patients as ≥75 years group.

As most published studies, older patients had tumors with more favorable biologic profiles. The tumors of older patients were more frequently estrogen or progesterone receptor positive (P > 0.05). Older patients had more tumors that were c-erbB2 negative (P > 0.05) and low Ki-67 levels (P > 0.05), compared with younger patients. However, patients aged ≥75 years had less tumors with normal p53 than younger patients (P > 0.001) (Table 2). 3.3. Comorbid illness

3.1. Pathological characteristics Table 1 summarizes tumor characteristics of patients by age group. Women aged ≥75 years had larger tumors

As expected, the older the patients, the higher the likelihood that the patients had comorbidities (P > 0.001) (Table 3). Hypertension was the most common comorbid illness in all

Table 1 Pathological characteristics of patients by age group. Age group

60–64 years, no. (%)

65–69 years, no. (%)

70–74 years, no. (%)

≥75 years, no. (%)

χ2

P

Histological type Ductal Lobular Mucinous Medullary Other

264(90.1) 10(3.4) 11(3.8) 3(1.0) 5(1.7)

229(91.6) 6(2.4) 8(3.2) 3(1.2) 4(1.6)

143(88.8) 4(2.5) 10(6.2) 3(1.9) 1(0.6)

124(76.5) 6(3.7) 16(9.9) 2(1.2) 14(8.6)

32.51

<0.001

Pathological tumor size T1 119(40.6) T2 146(49.8) T3 13(4.4) T4 3(1.0) Not available 12(4.1)

102(40.8) 122(48.8) 10(4.0) 3(1.2) 13(5.2)

69(42.9) 84(52.2) 3(1.9) 1(0.6) 4(2.5)

49(30.2) 85(52.5) 14(8.6) 9(5.6) 5(3.1)

23.22

<0.01

Pathological nodes N N+ 1–3 N+ 4–9 N+ ≥10 Not available

181(61.8) 65(22.2) 28(9.6) 18(6.1) 1(0.3)

161(64.4) 53(21.2) 21(8.4) 13(5.2) 2(0.8)

104(64.6) 28(17.4) 20(12.4) 8(5.0) 1(0.6)

93(57.4) 37(22.8) 7(4.3) 11(6.8) 14(8.6)

8.70

>0.05

Tumor grade G1 G2 G3 Not available

7(2.4) 172(58.7) 46(15.7) 68(23.2)

1(0.4) 157(62.8) 37(14.8) 55(22.0)

4(2.5) 90(55.9) 30(18.6) 37(23.0)

3(1.9) 84(51.9) 26(16.0) 49(30.2)

6.59

>0.05

Peritumoral invasion Present Absent Not available

44(15.0) 236(80.5) 13(4.4)

31(12.4) 205(82.0) 14(5.6)

16(9.9) 141(87.6) 4(2.5)

16(9.9) 141(87.0) 5(3.1)

4.04

>0.05

C.-D. Ma et al. / Critical Reviews in Oncology/Hematology 71 (2009) 258–265

261

Table 2 Biological characteristics of patients by age group. Age group

60–64 years, no. (%)

65–69 years, no. (%)

70–74 years, no. (%)

≥75 years, no. (%)

χ2

P

c-erbB2 −−− +−− ++− +++ Not available

156(53.2) 52(17.7) 30(10.2) 38(13.0) 17(5.8)

136(54.4) 43(17.2) 27(10.8) 34(13.6) 10(4.0)

103(64.0) 30(18.6) 15(9.3) 9(5.6) 4(2.5)

111(68.5) 22(13.6) 14(8.6) 7(4.3) 8(4.9)

21.52

<0.05

ER Positive Negative Not available

163(55.6) 115(39.2) 15(5.1)

153(61.2) 87(34.8) 10(4.0)

110(68.3) 47(29.2) 4(2.5)

107(66.0) 47(29.0) 8(4.9)

7.99

<0.05

PgR Positive Negative Not available

125(42.7) 153(52.2) 15(5.1)

134(53.6) 106(42.4) 10(4.0)

99(61.5) 58(36.0) 4(2.5)

97(59.9) 57(35.2) 8(4.9)

19.45

<0.001

P53 −−− +−− ++− +++ Not available

167(57.0) 52(17.7) 37(12.6) 17(5.8) 20(6.8)

112(44.8) 79(31.6) 30(12.0) 10(4.0) 19(7.6)

72(44.7) 59(36.6) 12(7.5) 9(5.6) 9(5.6)

55(34.0) 65(40.1) 20(12.3) 6(3.7) 16(9.9)

39.95

<0.001

Ki-67 0–30 31–100 Not available

93(31.7) 60(20.5) 140(47.8)

82(32.8) 32(12.8) 136(54.4)

34(21.1) 14(8.7) 113(70.2)

39(24.1) 8(4.9) 115(71.0)

9.51

<0.05

age groups. The incidence of cardiovascular disease was higher in older patients (P > 0.05). The percentage of patients with two or more comorbidities was different according to age (P > 0.05). 3.4. Local and systemic treatments Of the 866 patients, 88.6% underwent modified radical mastectomy; women 75 and older were less likely to undergo modified radical mastectomy or radical mastectomy, more likely to undergo simple mastectomy or breast-conserving surgery, compared with their younger counterparts (P > 0.001) (Table 4). Older patients received radiotherapy less frequently (P > 0.05). Women in older group were more likely to receive no adjuvant systemic therapy than women in younger group (P > 0.001). Patients aged ≥75 years were less likely to receive adjuvant chemotherapy, more likely to receive endocrine therapy than younger patients (P > 0.001) (Table 4).

3.5. Multinomial and binary logistic regression Multinomial logistic regression model showed that there were statistical associations between lymph node status, ER and PgR status, comorbidities and age and the choice of adjuvant systemic therapies (Table 5). Adjusting for ER and PgR status, lymph node status and comorbidities, there was still a significant association between age and the probability to receive systemic therapy. A woman in 70–74 years group, or in 65–69 years group, or in 60–64 years group has an odds ratio (OR) of 3.7 (95% confidence interval [CI], 1.4, 10.1), 13.3 (95% CI, 5.3, 33.4), 34.2 (95% CI, 13.1, 89.2), respectively, of receiving adjuvant chemotherapy alone, compared with a woman in 75 years and older group (Table 5). Binary logistic regressions showed that whether patients received postoperative radiotherapy or not was influenced by the type of surgery, axillary lymph node status and age (Table 6).

Table 3 Comorbid illness of patients by age group. Age group

60–64 years, no. (%)

65–69 years, no. (%)

70–74 years, no. (%)

≥75 years, no. (%)

χ2

P

Comorbid illness Hypertension Diabetes Cardiovascular disease ≥2 comorbidities No comorbidity

83(28.3) 29(9.9) 25(8.5) 37(12.6) 174(59.4)

77(30.8) 26(10.4) 24(9.6) 37(14.8) 123(49.2)

66(41.0) 26(16.1) 24(14.9) 36(22.4) 64(39.8)

59(36.4) 23(14.2) 26(16.0) 33(20.4) 63(38.9)

8.96 5.19 8.59 9.48 24.79

<0.05 >0.05 <0.05 <0.05 <0.001

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Table 4 Local and systemic treatments of patients by age group. Age group

60–64 years, no. (%)

65–69 years, no. (%)

70–74 years, no. (%)

≥75 years, no. (%)

Surgery MRM RM Mastectomy BCS

258(88.1) 24(8.2) 1(0.3) 10(3.4)

219(87.6) 24(9.6) 3(1.2) 4(1.6)

152(94.4) 6(3.7) 1(0.6) 2(1.2)

138(85.2) 3(1.9) 9(5.6) 12(7.4)

Radiotherapy Yes No

38(13.0) 255(87.0)

19(7.6) 231(92.4)

9(5.6) 152(94.4)

3(1.9) 159(98.1)

Systemic therapy No treatment CTa only HTb only CT + HT

32(10.9) 113(38.6) 40(13.7) 108(36.9)

71(28.4) 78(31.2) 36(14.4) 65(26.0)

52(32.3) 20(12.4) 53(32.9) 36(22.4)

71(43.8) 8(4.9) 68(42.0) 15(9.3)

a b

χ2

P

45.53

<0.001

19.55

<0.001

192.89

<0.001

Chemotherapy. Hormonal therapy.

Multinomial regression model also revealed that age was associated independently with the type of surgery patients received (Table 7).

4. Discussion This study described tumor characteristics and treatment patterns of elderly patients with early breast cancer. We compared the features, treatment patterns of women age ≥75 years with those of women age 70–74 years, 65–69 years and 60–64 years, and explored the factors influencing local and systemic adjuvant treatment decisions. In this study, we found that older women had a greater frequency of tumors with more indolent histologies. We also found the distribution of histological subtypes in our elderly

patients is slightly different from those of most published studies [5,8,17]. Older women in our series had more tumors with mucinous carcinoma and other histological subtypes. In addition, the percentage of our older patients with lobular carcinoma was obviously lower than those reported by Diab [8] and Gennari et al. [17]. Although older patients had larger tumors at diagnosis than younger patients, we did not find statistically significant difference in the percentage of axillary node involvement with increasing age. This is in agreement with Mustacchi et al. [22], who found no age-related difference in patients ≥65 years old, not in agreement with Daidone [11] and Gennari et al. [17], who found more axillary node involvement in older patients, and not with Bonnier et al. [23] and Fisher et al. [24] and Singh et al. [25], who observed less axillary lymph node involvement in elderly patients. The heterogeneous report-

Table 5 Factors influencing adjuvant systemic treatments of patients. Systemic therapya

60–64 years 65–69 years 70–74 years ≥75 years N N+ 1–3 N+ 4–9 N+ ≥10 ER and PgR ER or PgR+ ER and PgR+ ≥2 comorbidities Absent Present a b c d e

CTb only

HTc only

ORd

95%

34.2 13.3 3.7 1 0.3 1.1 0.9 1 17.6 16.8 1

13.1, 89.2 5.3, 33.4 1.4, 10.1

2.5 1

CIe

0.1, 0.8 0.4, 3.5 0.2, 3.1 6.3, 38.7 6.4, 43.9

1.2, 5.4

CT and HT

OR

95% CI

OR

95% CI

1.9 0.4 1.0 1 5.6 5.0 2.0 1 0.0 0.7 1

0.9, 4.0 0.2, 0.7 0.5, 2.0

42.4 5.4 4.6 1 0.3 0.8 1.1 1 0.0 0.8 1

17.1, 105.2 2.4, 12.0 2.0, 11.1

1.6 1

The reference category for systemic therapy (multinomial logistic regression) is “no CT or HT”. Chemotherapy. Hormonal therapy. Odds ratio. Confidence interval.

1.1, 28.6 0.9, 27.5 0.3, 14.9 0.0, 0.0 0.4, 1.3

0.8, 3.0

1.5 1

0.1, 0.7 0.3, 2.3 0.3, 3.9 0.0, 0.0 0.4, 1.5

0.8, 3.0

C.-D. Ma et al. / Critical Reviews in Oncology/Hematology 71 (2009) 258–265 Table 6 Factors influencing radiotherapy of patients. Radiotherapya

ORb

95% CIc

60–64 years 65–69 years 70–74 years ≥75 years N N+ 1–3 N+ 4–9 N+ ≥10 MRM RM Mastectomy BCS

8.3 5.1 3.6 1 0.1 0.2 0.6 1 0.1 0.1 0.4 1

2.3, 30.1 1.3, 19.4 0.9, 15.0

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might account for the difference. The cut-off value for Ki67 labeling index was different, from 10%, like Mustacchi et al. [22], to 20%, like Gennari et al. [17], and to 30%, like Molino et al. [18]. We found that older patients had lower Ki-67 levels at the cut-off point of 30%. However, Ki-67 labeling index was available only for 30% of elderly patients in our study, larger studies are needed to conform our results. Our data demonstrate that modified radical mastectomy is the most common type of surgery for elderly patients, and patients age ≥75 years received relatively conservative surgery more frequently, but the proportions of patients undergoing MRM and RM were similar in 60–64 years old, 65–69 years old and 70–74 years old group. Previous studies showed that breast-conserving surgery was used to 50–80% of elderly patients [17,22,30]. In our institute, patients age ≥60 years old rarely underwent breast-conserving surgery, only about 1–7% of patients received such a therapy. The reasons for this significant difference might be multifactorial and might mainly include patient preferences and clinician attitudes [31]. Even though older patients had larger tumors at diagnosis, postoperative radiotherapy was more likely to be omitted for our older patients. This is in line with most published reports [5,32,33]. Adjuvant chemotherapy was administered to 14% of the patients aged ≥75 years, and increasing age predicted the decreased proportion of our elderly patients receiving chemotherapy. Numerous retrospective studies have shown 5–30% of actual administration of adjuvant chemotherapy to elderly women [34]. Older women are less likely to be treated with adjuvant chemotherapy because of many factors, including the lack of data, patient comorbidities, and concerns over toxicity [35]. In our cohort, endocrine therapy alone significantly increased with age, with 14%, 14%, 33%, and 42% of patients 60–64 years old, 65–69 years old, 70–74 years old, and 75 years or older, respectively, receiving such a therapy; 69% of patients with hormone receptor-positive tumors in ≥75 years age group received endocrine treatment. Because most breast cancers in the elderly are hormone responsive, hormonal therapy remains the mainstay of systemic treatment in the adjuvant settings [36]. Also because it is less toxic, hormonal treatment is more likely to be administered to older patients.

0.1, 0.3 0.1, 0.5 0.3, 1.6 0.0, 0.2 0.0, 0.3 0.0, 4.3

a The reference category for radiotherapy (binary logistic regression) is “no radiotherapy”. b Odds ratio. c Confidence interval.

ings of lymph node involvement across series need further study [17,18]. We found that women aged ≥75 years referred for surgery had favorable biologic tumor profile, compared with women in other groups. This is consistent with most published results [5,8,17,18,26,27]. However, the percentage of ER-positive tumors in our elderly patients was slightly different from those of other studies [8,17,18]. Previous studies showed that the proportion of ER-positive tumors was higher in older patients, this amounts to 81–95% in women aged >65 years [5,8,22]. On the other hand, the percentage of our elderly patients with ER-positive tumors was lower than 70% even in ≥75 years age group. Another study, including 1052 Chinese breast cancer patients, revealed that ER was positive in 61.6% of postmenopausal women [28]. Sughayer et al. [29] also reported that the prevalence of hormone receptor positivity in breast cancer of Jordanian women was lower than that of western populations. Those results suggest that Asian elderly patients could have less ER-positive tumors than western patients. In our research, older patients had less tumors with negative P53 protein, which is different from Diab [5], who found that older patients had more tumors with normal P53 protein. Older patients in our series had more tumors with P53 (+), not P53 (++ ∼ +++), and P53 protein expression was determined by different immunostaining methods, these Table 7 Factors influencing surgical treatment of patients. Surgerya

60–64 years 65–69 years 70–74 years ≥75 years a b c

MRM

RM

ORb

CIc

95%

2.2 4.6 6.7 1

1.0, 5.1 1.5, 14.7 1.5, 30.5

Mastectomy

OR

95% CI

OR

95% CI

9.0 22.9 12.3 1

2.1, 39.0 4.4, 119.6 1.6, 94.6

0.1 1.0 0.7 1

0.0, 1.2 0.2, 5.4 0.1, 8.7

The reference category for surgery (multinomial logistic regression) is “breast-conserving surgery”. Odds ratio. Confidence interval.

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As expected, comorbidities such as hypertension and cardiovascular disease were more often recorded in our older patients, compared with younger patients. Because of the retrospective nature of this study, it was difficult to apply standard comorbidity indexes, such as Charlson’s scale [21] or the CIRS-G scale [37], to our patients. Alternatively, we simply classified comorbid conditions as absent or present. We found that concomitant conditions did not influence the decision of local treatments but affected the choice of adjuvant systemic treatments (Tables 5–7). Our data confirm that age was associated strongly and independently with adjuvant chemotherapy decision, after adjustment for lymph node status, ER and PgR status, comorbidities. The results of the current study are consistent with those from previous reports that older women with breast carcinoma were less likely than younger women to receive adjuvant chemotherapy [17,32,38,39]. These studies and the current one illuminate the complexity of treating older patients with breast cancer. Binary logistic and multinomial regressions also showed that age was strongly associated with the choice of local treatments, independent of other factors. Further studies clearly are needed to determine the underlying reasons for age effect and to explore strategies that will optimize the utilization of multimodality therapy in this growing patient population [38]. In conclusion, our results confirm that the biological behavior of breast cancer in older patients is more favorable, compared with their younger counterparts. Age is independently associated with different treatment patterns, elderly women appear to receive less aggressive treatments.

Conflicts of interest The authors indicated no potential conflict of interest.

Reviewers Dr. Umberto Basso, Full time Medical Oncologist, Istituto Oncologico Veneto IOV-IRCCS, Medical Oncology, via Gattamelata 64, I-35128 Padova, Italy. Prof. Hans Wildiers, University Hospital Gasthuisberg, Dept. of Medical Oncology, Herestraat 49, B-3000 Leuven, Belgium.

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Biography Zhen-Zhou Shen is a tenure professor of Department of Surgery at the Cancer Hospital of Fudan University. He is a member of the American Society of Surgery, and an executive committee member of the Asian Breast Cancer Society. Professor Shen is also the Honorable Chairman of the Chinese Anticancer Association and Chinese Breast Cancer Society. He has published more than 150 articles and has been the recipient of the Science and Technology Progress Award for many times.