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Surgery improves breast cancer-specific survival in octogenarians with early-stage breast cancer
ORIGINAL RESEARCH International Journal of Surgery 11 (2013) 554e557
Contents lists available at SciVerse ScienceDirect
International Journal of Surgery journal homepage: www.theijs.com
Original research
Surgery improves breast cancer-specific survival in octogenarians with early-stage breast cancer Tomás Cortadellas*, Andrea Gascón, Octavi Córdoba, Jordi Rabasa, Robert Rodríguez, Martin Espinosa-Bravo, Antonio Esgueva, Isabel T. Rubio, Jordi Xercavins, Antonio Gil Breast Cancer Unit, Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history: Received 21 March 2013 Received in revised form 9 May 2013 Accepted 17 May 2013 Available online 27 May 2013
Introduction: No consensus exists on optimum therapy for older cancer patients. This singlecentre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. Methods: Data of all elderly breast cancer patients (80 years) with primary breast cancer treated at out institution between 1990 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the KaplaneMeier method. Results: The study population consisted of 259 patients (median age 84 years). There were 189 (73%) patients with early stage disease (I, IIA, IIB) and 70 (27%) with locally advanced disease (IIIA, IIIB, IIIC). A total of 175 (67.7%) patients underwent surgical treatment and 84 (32.4%) received primary endocrine treatment. Patients were followed for a median of 65 months. In patients with early stages, the mean breast cancer-specific survival was 108 months (95% CI 101e115) in the surgical group and 50 months (95% CI 39e61) in the non-surgical group (P < 0.01), whereas patients with locally advanced breast cancer breast cancer-specific survival was similar for the surgical and non-surgical groups. Breast cancerspecific survival and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those with suboptimal surgery. Conclusion: In women 80 years with early-stage breast cancer, standard surgical treatment as compared with non-surgical therapy was associated with a better breast cancer-specific. Ó 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Breast cancer Octogenarian patients Breast cancer-specific survival Standard surgical treatment Primary endocrine therapy
1. Introduction Increasing life expectancy in the United States and European populations has been associated with an increase in the incidence of breast cancer in elderly women. Ageing remains one of the single greatest risk factors for the development of new breast cancer, and more than 30% of breast cancers occur after age of 75.1,2 Breast cancer management in elderly women remains a complex problem for clinicians and there is disagreement about the optimum treatment. In spite of apparently favourable prognostic factors, such as low grade tumour types, smaller incidence of axillary lymph node
* Corresponding author. Tel.: þ34 93 4893174; fax: þ34 93 2746715. E-mail addresses: [email protected] (T. Cortadellas), [email protected] (A. Gascón), [email protected] (O. Córdoba), [email protected] (J. Rabasa), [email protected] (R. Rodríguez), [email protected] (M. Espinosa-Bravo), [email protected] (A. Esgueva), [email protected] (I.T. Rubio), [email protected] (J. Xercavins), [email protected] (A. Gil).
involvement and vascular invasion, estrogen receptor-positive disease, and less aggressive tumour biology,3e6 elderly breast cancer patients often receive less than the standard of care when compared with their younger counterparts.7,8 Primary endocrine therapy is sometimes substituted for operation, and axillary surgery, adjuvant chemotherapy and adjuvant radiotherapy are frequently omitted.9 A Cochrane review of surgery versus primary endocrine therapy for operable primary breast cancer in women 70 years or over showed that surgery controls breast cancer better than tamoxifen alone with significant differences in progressionfree survival, but does not extend overall survival.10 Moreover, much of the literature defines “elderly” very broadly, including women as young as 65 or even excluding women over 80 from studies focused on older breast cancer patients. There is a paucity of data for the “oldest old” patients and to date differences in outcome between surgery and primary endocrine treatment in breast cancer octogenarians has been poorly assessed.9,11e13 This study was conducted to review management and outcomes for women 80 years and older treated for breast cancer at our
1743-9191/$ e see front matter Ó 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijsu.2013.05.032
ORIGINAL RESEARCH T. Cortadellas et al. / International Journal of Surgery 11 (2013) 554e557
institution. The objective of the study was to assess differences in survival between surgically and non-surgically treated patients as well as between patients undergoing standard versus suboptimal surgical treatment. 2. Patients and methods We conducted a retrospective study of all elderly breast cancer patients (80 years) with primary breast cancer treated at out institution between 1995 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Data were collected from the medical records. Follow-up information (vital status) was obtained from medical charts or by telephone contact with the patients, their family or their family physician. Causes of death were also determined from medical records by telephone or from main data resources when available. Institutional review board approval was obtained prior to the commencement of this retrospective study. Written informed consent of the patients was not required. Data collected included demographic details, histological type, age at the initial diagnosis, clinical stage, receptor status, presence of lymphovascular invasion, treatment modalities including surgical resection, adjuvant chemotherapy, endocrine therapy and radiotherapy. The first sentinel lymph node biopsy performed in this series of patients occurred in 2001. Patients were divided into two groups, those who received primary surgical treatment and those who received primary endocrine therapy. Patients in both groups were stratified into early (I, IIA, IIB) and locally advanced (III) stages. In our unit, all patients of all ages diagnosed with breast cancer stages I, II, and III are candidates to surgical treatment except if there are anaesthetic contraindications. Patients >80 years of age were informed on the non-surgical alternative of endocrine therapy with good results. Therefore, the decision to be treated conservatively mainly depended on the decision of the patients or relatives, and to a lower extent by a formal contraindication on the part of the anaesthetist. Surgically-treated patients were also classified into those undergoing standard surgical treatment fulfilling oncological criteria, including mastectomy, simple mastectomy and sentinel lymph node biopsy, margin-free lumpectomy and sentinel lymph node biopsy or margin-free lumpectomy and axillary dissection, and those undergoing suboptimal surgical treatment, including mastectomy or margin-free lumpectomy without assessment of axillary lymph node involvement, resection of palpable lymph nodes only or axillary sampling. 2.1. Statistical analysis Differences in demographic and clinical variables between the surgical and nonsurgical groups were assessed with the chi-square (c2) test for categorical variables and the Student’s t test or the ManneWhitney U test for quantitative variables. Statistical significance was set at P < 0.05. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the KaplaneMeier method by using SPSS software (version 17.0; SPSS Inc., Chicago, IL). Differences in survival were assessed with log-rank test.
3. Results A total of 360 patients aged 80 years presented with primary breast cancer between 1995 and 2009. Of these, 45 patients had carcinoma in situ (stage 0, n ¼ 20) or advanced disease (stage IV, n ¼ 25) and were excluded from the study. Fifty-six patients in whom information regarding vital status at the time of analysis could not be obtained were also excluded. The study population consisted of 259 patients. Median age at diagnosis was 84 years (range, 80e99 years). There were 189 (73%) patients with early stages of disease and 70 (27%) with locally advanced disease. A total of 175 (67.7%) patients underwent surgical treatment, and the other 84 (32.4%) received primary endocrine treatment. The distribution of patients in the surgical and non-surgical groups in relation to clinical stages is shown in Table 1. Patients in the surgical group were younger (mean age 83.8 years, 95% confidence interval [CI] 83.3e84.3) than those in the non-surgical group (mean age 85.2 years, 95% CI 84.5e85.9) but differences were not statistically significant. When the surgical and non-surgical groups were compared, significant differences in the percentage of patients with positive estrogen receptors (78.8% vs 86.9%), presence of lymphovascular invasion (86.8% vs 88.1%), and use of chemotherapy (17.1% vs 11.9%) and radiotherapy (24% vs 19%)
555
Table 1 Distribution of breast cancer stages in the surgical and non-surgical groups. Stage
Total patients
Early stages I 40 IIA 90 IIB 59 Locally advanced IIIA 12 IIIB 56 IIIC 2
Primary surgical treatment (n ¼ 175)
Primary endocrine therapy (n ¼ 84)
33 (82.5) 74 (82.2) 43 (72.9)
7 (17.5) 16 (17.8) 16 (27.1)
9 (75) 15 (26.8) 1 (50)
3 (25) 41 (73.2) 1 (50)
Percentages in parenthesis.
were not found. Eighty percent of patients in the surgical groups received hormonal treatment (tamoxifen, aromatase inhibitors) as compared with 75% in the non-surgical group. Patients were followed for a median of 65 months. A total of 80 patients died of breast cancer (31%) and the remaining 179 patients (69%) of other causes. In the group of 189 patients with early stages of breast cancer, there were 150 (79.4%) patients in the surgical group and the remaining 39 in the non-surgical group. As shown in Fig. 1, the mean breast cancer-specific survival was 108 months (95% CI 101e115) in the surgical group of patients with early-stage disease as compared with 50 months (95% CI 39e61) in the nonsurgical group (P < 0.01). However, in patients with locally advanced breast cancer (n ¼ 70), the mean breast cancer-specific survival was similar for patients in the surgical (n ¼ 25) and nonsurgical (n ¼ 45) groups (76 months, 95% CI 62e89 vs 68 months (95% CI 49e86) (P ¼ 0.071). Of the 175 patients treated surgically, 150 (85.7%) received standard or optimal surgical treatment. In the remaining 25 patients, surgical operation was considered suboptimal. As shown in Fig. 2, breast cancer-specific survival was significantly better among patients who underwent standard surgical treatment (108 months, 95% CI 101e115) than among those with suboptimal surgical treatment (71 months, 95% CI 71e108) (P ¼ 0.008). Differences in disease-free survival were also observed (110 months, 95% CI 102e 118 for standard surgery vs 77 months, 95% CI 60e95 for suboptimal surgery) (P ¼ 0.04) (Fig. 3). 4. Discussion Breast cancer management in elderly women remains a complex problem for clinicians and there is disagreement about the optimum treatment. Moreover, it is often assumed that therapy
Fig. 1. Differences in breast cancer-specific survival between the surgical and nonsurgical treatment groups.
ORIGINAL RESEARCH 556
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Fig. 2. Breast cancer-specific survival was significantly longer among patients who underwent standard surgical treatment than among patients with suboptimal surgical treatment.
may be more harmful and may provide less benefit to elderly breast cancer patients. Part of this controversy results from some common misconceptions, such as the elderly have a limited life expectancy because of comorbid conditions, or that breast cancer mortality among the elderly is a marginal problem because of the increased risk of death from other causes. In a series of 134 women 80 years old reported by Cyr et al.,12 only 4% died of breast cancer. In a retrospective series of 100 patients more than 70 years old with breast cancer who underwent radical surgery between 1990 and 1998, de la Haba Rodríguez et al.14 progression of breast cancer was the main cause of death. In the study of Evron et al.13 of 135 women with localized breast cancer at age 80 years or older, breast cancer was the cause of death in 35.3% of the patients, which is consistent with 31% of deaths due to breast cancer found in our study. Bouchardy et al.11 in a review of the clinical files of 407 breast cancer patients aged 80 years, 5-year specific breast cancer survival was 51% for tamoxifen alone as compared with 82% for mastectomy and 90% for breast-conservative surgery plus adjuvant treatment. The authors conclude that undertreatment of elderly patients with breast cancer strongly decreases specific survival, which is in agreement with results of the present study. In the GRETA trial,15 surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as
compared with tamoxifen alone; however, in those patients who received the primary endocrine treatment, there was a high rate of local progression. Also, better survival in the surgical treatment group when compared with the primary endocrine treatment group was documented in the study of Rao et al.9 In our study, breast cancer-specific survival was significantly better in the surgical group but only in patients with early-stage breast cancer, whereas differences in the modality of treatment in patients with locally advanced breast cancer were not found. The role of radiotherapy in older women with breast cancer is controversial because of eventual serious adverse effects. In our study, 22.4% received radiation therapy but different studies have shown the underuse of radiation therapy in older breast cancer patients.16,17 In a study of 636 women who were 70 years of age or older with clinical stage I and estrogen-receptor-positive breast carcinoma treated by lumpectomy, tamoxifen plus radiation therapy versus tamoxifen alone showed similar results with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival. The only significant difference between the two groups was in the rate of local or regional recurrence at 5 years (1% in the group given tamoxifen plus irradiation and 4% in the group given tamoxifen alone, P < 0.001).18 In contrast, in a cohort of 1837 women having operations for stage I or II breast cancer aged 65 years or older, patients receiving breastconservative surgery without radiation therapy were twice as likely to die of breast cancer compared with women receiving mastectomy.19 Breast cancer mortality rates were similar between women receiving breast-conservative surgery plus radiotherapy and women receiving mastectomy.19 We found that standard surgical treatment in octogenarian breast cancer patients as compared with suboptimal surgical treatment was associated with a better breast cancer-specific survival and disease-free survival. However, in the study of Evron et al.13 standard local treatment that comprised modified radical mastectomy or margin-free lumpectomy and axillary dissection followed by radiation showed no significant differences in overall survival and breast cancer-specific survival as compared with less than standard local treatment where either radiotherapy or axillary dissection or both were withheld. Limitations of the study include the retrospective nature and the fact that data on comorbidities were not consistently registered. However, this study has highlighted significant breast cancerspecific survival in the surgical treatment group as compared with primary endocrine therapy for elderly patients with earlystage breast cancer. In agreement with other studies20 there is no reason why age should be a consideration in the management of breast cancer. Breast cancer octogenarians should receive optimal oncological surgical treatment as younger patients. Primary endocrine therapy may be provided to patients who refuse or are unfit for surgery. Involvement of a multidisciplinary team including multidimensional geriatric evaluation permits a better selection and individualized therapeutic decision for each patient. Ethical approval Institutional review board approval was obtained prior to the commencement of this retrospective study. Written informed consent of the patients was not required. No ethical approvement was necessary. Funding None.
Fig. 3. Differences in disease-free survival for standard surgical treatment and suboptimal surgery.
Author contribution Conception and design: Tomas Cortadellas, IT Rubio, Jordi Xercavins, Antonio Gil.
ORIGINAL RESEARCH T. Cortadellas et al. / International Journal of Surgery 11 (2013) 554e557
Data collection: Jordi Rabasa, Andrea Gascón, Octavi Cordoba. Data analysis and interpretation: Antonio Esgueva, Martín Espinosa-Bravo. Conflict of interests None. Acknowledgement The authors thank Marta Pulido, MD, for editing the manuscript and editorial assistance. References 1. Louwman WJ, Voogd AC, van Dijck JA, et al. On the rising trends of incidence and prognosis for breast cancer patients diagnosed 1975e2004: a long-term populationbased study in southeastern Netherlands. Cancer Causes Control 2008;19:97e106. 2. Thomson CS, Brewster DH, Dewar JA, Twelves CJ. Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment. Eur J Cancer 2004;40:743e53. 3. Fisher CJ, Egan MK, Smith P, Wicks K, Millis RR, Fentiman IS. Histopathology of breast cancer in relation to age. Br J Cancer 1997;75:593e6. 4. Hainsworth PJ, Henderson MA, Bennett RC. Breast cancer in the elderly: pattern of disease. Aust N Z J Surg 1991;61:892e7. 5. Godolphin W, Elwood JM, Spinelli JJ. Estrogen receptor quantitation and staging as complementary prognostic indicators in breast cancer: a study of 583 patients. Int J Cancer 1981;28:677e83. 6. Diab SG, Elledge RM, Clark GM. Tumor characteristics and clinical outcome of elderly women with breast cancer. J Natl Cancer Inst 2000;92:550e6. 7. Satariano WA. Comorbidity and functional status in older women with breast cancer: implications for screening, treatment, and prognosis. J Gerontol 1992; Nov;47. Spec No:24e31.
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8. Wyld L, Reed M. The role of surgery in the management of older women with breast cancer. Eur J Cancer 2007;43:2253e63. 9. Rao VS, Jameel JK, Mahapatra TK, McManus PL, Fox JN, Drew PJ. Surgery is associated with lower morbidity and longer survival in elderly breast cancer patients over 80. Breast J 2007;13:368e73. 10. Hind D, Wyld L, Reed MW. Surgery, with or without tamoxifen, vs tamoxifen alone for older women with operable breast cancer: Cochrane review. Br J Cancer 2007;96:1025e9. 11. Bouchardy C, Rapiti E, Fioretta G, et al. Undertreatment strongly decreases prognosis of breast cancer in elderly women. J Clin Oncol 2003; 21:3580e7. 12. Cyr A, Gillanders WE, Aft RL, Eberlein TJ, Margenthaler JA. Breast cancer in elderly women (80 years): variation in standard of care? J Surg Oncol 2011;103:201e6. 13. Evron E, Goldberg H, Kuzmin A, Gutman R, Rizel S, Sella A, et al. Breast cancer in octogenarians. Cancer 2006;106:1664e8. 14. de la Haba Rodríguez JR, Méndez Vidal MJ, Gómez España A, et al. Adjuvant treatment in elderly patients with breast cancer: critical review of clinical practice. Am J Clin Oncol 2003;26:398e401. 15. Mustacchi G, Ceccherini R, Milani S, et al. Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial. Ann Oncol 2003;14: 414e20. 16. Litvak DA, Arora R. Treatment of elderly breast cancer patients in a community hospital setting. Arch Surg 2006;141:985e90. 17. Smith GL, Xu Y, Shih YC, Giordano SH, et al. Breast-conserving surgery in older patients with invasive breast cancer: current patterns of treatment across the United States. J Am Coll Surg 2009;209:425e33. e2. 18. Hughes KS, Schnaper LA, Berry D, et al. Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 2004;351:971e7. 19. Yood MU, Owusu C, Buist DS, et al. Mortality impact of less-than-standard therapy in older breast cancer patients. J Am Coll Surg 2008;206:66e75. 20. Gazet JC, Sutcliffe R. A randomised trial comparing tamoxifen vs. surgery in patients over the age of 70 with operable breast cancer e final results after 28 years of follow-up. Eur J Surg Oncol 2011;37:754e7.
Contents lists available at SciVerse ScienceDirect
International Journal of Surgery journal homepage: www.theijs.com
Original research
Surgery improves breast cancer-specific survival in octogenarians with early-stage breast cancer Tomás Cortadellas*, Andrea Gascón, Octavi Córdoba, Jordi Rabasa, Robert Rodríguez, Martin Espinosa-Bravo, Antonio Esgueva, Isabel T. Rubio, Jordi Xercavins, Antonio Gil Breast Cancer Unit, Department of Obstetrics and Gynecology, Hospital Universitari Vall d’Hebron, Universitat Autònoma de Barcelona, Passeig Vall d’Hebron 119-129, E-08035 Barcelona, Spain
a r t i c l e i n f o
a b s t r a c t
Article history: Received 21 March 2013 Received in revised form 9 May 2013 Accepted 17 May 2013 Available online 27 May 2013
Introduction: No consensus exists on optimum therapy for older cancer patients. This singlecentre study was conducted to review the treatment and outcomes for octogenarian women treated for breast cancer. Methods: Data of all elderly breast cancer patients (80 years) with primary breast cancer treated at out institution between 1990 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the KaplaneMeier method. Results: The study population consisted of 259 patients (median age 84 years). There were 189 (73%) patients with early stage disease (I, IIA, IIB) and 70 (27%) with locally advanced disease (IIIA, IIIB, IIIC). A total of 175 (67.7%) patients underwent surgical treatment and 84 (32.4%) received primary endocrine treatment. Patients were followed for a median of 65 months. In patients with early stages, the mean breast cancer-specific survival was 108 months (95% CI 101e115) in the surgical group and 50 months (95% CI 39e61) in the non-surgical group (P < 0.01), whereas patients with locally advanced breast cancer breast cancer-specific survival was similar for the surgical and non-surgical groups. Breast cancerspecific survival and disease-free survival were significantly better among patients who underwent standard surgical treatment than among those with suboptimal surgery. Conclusion: In women 80 years with early-stage breast cancer, standard surgical treatment as compared with non-surgical therapy was associated with a better breast cancer-specific. Ó 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.
Keywords: Breast cancer Octogenarian patients Breast cancer-specific survival Standard surgical treatment Primary endocrine therapy
1. Introduction Increasing life expectancy in the United States and European populations has been associated with an increase in the incidence of breast cancer in elderly women. Ageing remains one of the single greatest risk factors for the development of new breast cancer, and more than 30% of breast cancers occur after age of 75.1,2 Breast cancer management in elderly women remains a complex problem for clinicians and there is disagreement about the optimum treatment. In spite of apparently favourable prognostic factors, such as low grade tumour types, smaller incidence of axillary lymph node
* Corresponding author. Tel.: þ34 93 4893174; fax: þ34 93 2746715. E-mail addresses: [email protected] (T. Cortadellas), [email protected] (A. Gascón), [email protected] (O. Córdoba), [email protected] (J. Rabasa), [email protected] (R. Rodríguez), [email protected] (M. Espinosa-Bravo), [email protected] (A. Esgueva), [email protected] (I.T. Rubio), [email protected] (J. Xercavins), [email protected] (A. Gil).
involvement and vascular invasion, estrogen receptor-positive disease, and less aggressive tumour biology,3e6 elderly breast cancer patients often receive less than the standard of care when compared with their younger counterparts.7,8 Primary endocrine therapy is sometimes substituted for operation, and axillary surgery, adjuvant chemotherapy and adjuvant radiotherapy are frequently omitted.9 A Cochrane review of surgery versus primary endocrine therapy for operable primary breast cancer in women 70 years or over showed that surgery controls breast cancer better than tamoxifen alone with significant differences in progressionfree survival, but does not extend overall survival.10 Moreover, much of the literature defines “elderly” very broadly, including women as young as 65 or even excluding women over 80 from studies focused on older breast cancer patients. There is a paucity of data for the “oldest old” patients and to date differences in outcome between surgery and primary endocrine treatment in breast cancer octogenarians has been poorly assessed.9,11e13 This study was conducted to review management and outcomes for women 80 years and older treated for breast cancer at our
1743-9191/$ e see front matter Ó 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijsu.2013.05.032
ORIGINAL RESEARCH T. Cortadellas et al. / International Journal of Surgery 11 (2013) 554e557
institution. The objective of the study was to assess differences in survival between surgically and non-surgically treated patients as well as between patients undergoing standard versus suboptimal surgical treatment. 2. Patients and methods We conducted a retrospective study of all elderly breast cancer patients (80 years) with primary breast cancer treated at out institution between 1995 and 2009. Patients with carcinoma in-situ (stage 0) and advanced breast cancer (stage IV) were excluded. Data were collected from the medical records. Follow-up information (vital status) was obtained from medical charts or by telephone contact with the patients, their family or their family physician. Causes of death were also determined from medical records by telephone or from main data resources when available. Institutional review board approval was obtained prior to the commencement of this retrospective study. Written informed consent of the patients was not required. Data collected included demographic details, histological type, age at the initial diagnosis, clinical stage, receptor status, presence of lymphovascular invasion, treatment modalities including surgical resection, adjuvant chemotherapy, endocrine therapy and radiotherapy. The first sentinel lymph node biopsy performed in this series of patients occurred in 2001. Patients were divided into two groups, those who received primary surgical treatment and those who received primary endocrine therapy. Patients in both groups were stratified into early (I, IIA, IIB) and locally advanced (III) stages. In our unit, all patients of all ages diagnosed with breast cancer stages I, II, and III are candidates to surgical treatment except if there are anaesthetic contraindications. Patients >80 years of age were informed on the non-surgical alternative of endocrine therapy with good results. Therefore, the decision to be treated conservatively mainly depended on the decision of the patients or relatives, and to a lower extent by a formal contraindication on the part of the anaesthetist. Surgically-treated patients were also classified into those undergoing standard surgical treatment fulfilling oncological criteria, including mastectomy, simple mastectomy and sentinel lymph node biopsy, margin-free lumpectomy and sentinel lymph node biopsy or margin-free lumpectomy and axillary dissection, and those undergoing suboptimal surgical treatment, including mastectomy or margin-free lumpectomy without assessment of axillary lymph node involvement, resection of palpable lymph nodes only or axillary sampling. 2.1. Statistical analysis Differences in demographic and clinical variables between the surgical and nonsurgical groups were assessed with the chi-square (c2) test for categorical variables and the Student’s t test or the ManneWhitney U test for quantitative variables. Statistical significance was set at P < 0.05. Breast cancer-specific survival and disease-free survival for the different patient groups were analysed according to the KaplaneMeier method by using SPSS software (version 17.0; SPSS Inc., Chicago, IL). Differences in survival were assessed with log-rank test.
3. Results A total of 360 patients aged 80 years presented with primary breast cancer between 1995 and 2009. Of these, 45 patients had carcinoma in situ (stage 0, n ¼ 20) or advanced disease (stage IV, n ¼ 25) and were excluded from the study. Fifty-six patients in whom information regarding vital status at the time of analysis could not be obtained were also excluded. The study population consisted of 259 patients. Median age at diagnosis was 84 years (range, 80e99 years). There were 189 (73%) patients with early stages of disease and 70 (27%) with locally advanced disease. A total of 175 (67.7%) patients underwent surgical treatment, and the other 84 (32.4%) received primary endocrine treatment. The distribution of patients in the surgical and non-surgical groups in relation to clinical stages is shown in Table 1. Patients in the surgical group were younger (mean age 83.8 years, 95% confidence interval [CI] 83.3e84.3) than those in the non-surgical group (mean age 85.2 years, 95% CI 84.5e85.9) but differences were not statistically significant. When the surgical and non-surgical groups were compared, significant differences in the percentage of patients with positive estrogen receptors (78.8% vs 86.9%), presence of lymphovascular invasion (86.8% vs 88.1%), and use of chemotherapy (17.1% vs 11.9%) and radiotherapy (24% vs 19%)
555
Table 1 Distribution of breast cancer stages in the surgical and non-surgical groups. Stage
Total patients
Early stages I 40 IIA 90 IIB 59 Locally advanced IIIA 12 IIIB 56 IIIC 2
Primary surgical treatment (n ¼ 175)
Primary endocrine therapy (n ¼ 84)
33 (82.5) 74 (82.2) 43 (72.9)
7 (17.5) 16 (17.8) 16 (27.1)
9 (75) 15 (26.8) 1 (50)
3 (25) 41 (73.2) 1 (50)
Percentages in parenthesis.
were not found. Eighty percent of patients in the surgical groups received hormonal treatment (tamoxifen, aromatase inhibitors) as compared with 75% in the non-surgical group. Patients were followed for a median of 65 months. A total of 80 patients died of breast cancer (31%) and the remaining 179 patients (69%) of other causes. In the group of 189 patients with early stages of breast cancer, there were 150 (79.4%) patients in the surgical group and the remaining 39 in the non-surgical group. As shown in Fig. 1, the mean breast cancer-specific survival was 108 months (95% CI 101e115) in the surgical group of patients with early-stage disease as compared with 50 months (95% CI 39e61) in the nonsurgical group (P < 0.01). However, in patients with locally advanced breast cancer (n ¼ 70), the mean breast cancer-specific survival was similar for patients in the surgical (n ¼ 25) and nonsurgical (n ¼ 45) groups (76 months, 95% CI 62e89 vs 68 months (95% CI 49e86) (P ¼ 0.071). Of the 175 patients treated surgically, 150 (85.7%) received standard or optimal surgical treatment. In the remaining 25 patients, surgical operation was considered suboptimal. As shown in Fig. 2, breast cancer-specific survival was significantly better among patients who underwent standard surgical treatment (108 months, 95% CI 101e115) than among those with suboptimal surgical treatment (71 months, 95% CI 71e108) (P ¼ 0.008). Differences in disease-free survival were also observed (110 months, 95% CI 102e 118 for standard surgery vs 77 months, 95% CI 60e95 for suboptimal surgery) (P ¼ 0.04) (Fig. 3). 4. Discussion Breast cancer management in elderly women remains a complex problem for clinicians and there is disagreement about the optimum treatment. Moreover, it is often assumed that therapy
Fig. 1. Differences in breast cancer-specific survival between the surgical and nonsurgical treatment groups.
ORIGINAL RESEARCH 556
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Fig. 2. Breast cancer-specific survival was significantly longer among patients who underwent standard surgical treatment than among patients with suboptimal surgical treatment.
may be more harmful and may provide less benefit to elderly breast cancer patients. Part of this controversy results from some common misconceptions, such as the elderly have a limited life expectancy because of comorbid conditions, or that breast cancer mortality among the elderly is a marginal problem because of the increased risk of death from other causes. In a series of 134 women 80 years old reported by Cyr et al.,12 only 4% died of breast cancer. In a retrospective series of 100 patients more than 70 years old with breast cancer who underwent radical surgery between 1990 and 1998, de la Haba Rodríguez et al.14 progression of breast cancer was the main cause of death. In the study of Evron et al.13 of 135 women with localized breast cancer at age 80 years or older, breast cancer was the cause of death in 35.3% of the patients, which is consistent with 31% of deaths due to breast cancer found in our study. Bouchardy et al.11 in a review of the clinical files of 407 breast cancer patients aged 80 years, 5-year specific breast cancer survival was 51% for tamoxifen alone as compared with 82% for mastectomy and 90% for breast-conservative surgery plus adjuvant treatment. The authors conclude that undertreatment of elderly patients with breast cancer strongly decreases specific survival, which is in agreement with results of the present study. In the GRETA trial,15 surgery (radical or minimal) followed by adjuvant tamoxifen does not modify overall and breast cancer survival as
compared with tamoxifen alone; however, in those patients who received the primary endocrine treatment, there was a high rate of local progression. Also, better survival in the surgical treatment group when compared with the primary endocrine treatment group was documented in the study of Rao et al.9 In our study, breast cancer-specific survival was significantly better in the surgical group but only in patients with early-stage breast cancer, whereas differences in the modality of treatment in patients with locally advanced breast cancer were not found. The role of radiotherapy in older women with breast cancer is controversial because of eventual serious adverse effects. In our study, 22.4% received radiation therapy but different studies have shown the underuse of radiation therapy in older breast cancer patients.16,17 In a study of 636 women who were 70 years of age or older with clinical stage I and estrogen-receptor-positive breast carcinoma treated by lumpectomy, tamoxifen plus radiation therapy versus tamoxifen alone showed similar results with regard to the rates of mastectomy for local recurrence, distant metastases, or five-year rates of overall survival. The only significant difference between the two groups was in the rate of local or regional recurrence at 5 years (1% in the group given tamoxifen plus irradiation and 4% in the group given tamoxifen alone, P < 0.001).18 In contrast, in a cohort of 1837 women having operations for stage I or II breast cancer aged 65 years or older, patients receiving breastconservative surgery without radiation therapy were twice as likely to die of breast cancer compared with women receiving mastectomy.19 Breast cancer mortality rates were similar between women receiving breast-conservative surgery plus radiotherapy and women receiving mastectomy.19 We found that standard surgical treatment in octogenarian breast cancer patients as compared with suboptimal surgical treatment was associated with a better breast cancer-specific survival and disease-free survival. However, in the study of Evron et al.13 standard local treatment that comprised modified radical mastectomy or margin-free lumpectomy and axillary dissection followed by radiation showed no significant differences in overall survival and breast cancer-specific survival as compared with less than standard local treatment where either radiotherapy or axillary dissection or both were withheld. Limitations of the study include the retrospective nature and the fact that data on comorbidities were not consistently registered. However, this study has highlighted significant breast cancerspecific survival in the surgical treatment group as compared with primary endocrine therapy for elderly patients with earlystage breast cancer. In agreement with other studies20 there is no reason why age should be a consideration in the management of breast cancer. Breast cancer octogenarians should receive optimal oncological surgical treatment as younger patients. Primary endocrine therapy may be provided to patients who refuse or are unfit for surgery. Involvement of a multidisciplinary team including multidimensional geriatric evaluation permits a better selection and individualized therapeutic decision for each patient. Ethical approval Institutional review board approval was obtained prior to the commencement of this retrospective study. Written informed consent of the patients was not required. No ethical approvement was necessary. Funding None.
Fig. 3. Differences in disease-free survival for standard surgical treatment and suboptimal surgery.
Author contribution Conception and design: Tomas Cortadellas, IT Rubio, Jordi Xercavins, Antonio Gil.
ORIGINAL RESEARCH T. Cortadellas et al. / International Journal of Surgery 11 (2013) 554e557
Data collection: Jordi Rabasa, Andrea Gascón, Octavi Cordoba. Data analysis and interpretation: Antonio Esgueva, Martín Espinosa-Bravo. Conflict of interests None. Acknowledgement The authors thank Marta Pulido, MD, for editing the manuscript and editorial assistance. References 1. Louwman WJ, Voogd AC, van Dijck JA, et al. On the rising trends of incidence and prognosis for breast cancer patients diagnosed 1975e2004: a long-term populationbased study in southeastern Netherlands. Cancer Causes Control 2008;19:97e106. 2. Thomson CS, Brewster DH, Dewar JA, Twelves CJ. Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment. Eur J Cancer 2004;40:743e53. 3. Fisher CJ, Egan MK, Smith P, Wicks K, Millis RR, Fentiman IS. Histopathology of breast cancer in relation to age. Br J Cancer 1997;75:593e6. 4. Hainsworth PJ, Henderson MA, Bennett RC. Breast cancer in the elderly: pattern of disease. Aust N Z J Surg 1991;61:892e7. 5. Godolphin W, Elwood JM, Spinelli JJ. Estrogen receptor quantitation and staging as complementary prognostic indicators in breast cancer: a study of 583 patients. Int J Cancer 1981;28:677e83. 6. Diab SG, Elledge RM, Clark GM. Tumor characteristics and clinical outcome of elderly women with breast cancer. J Natl Cancer Inst 2000;92:550e6. 7. Satariano WA. Comorbidity and functional status in older women with breast cancer: implications for screening, treatment, and prognosis. J Gerontol 1992; Nov;47. Spec No:24e31.
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