- Email: [email protected]
Surgical management of breast cancer in the elderly patient
The American Journal of Surgery 182 (2001) 359 –364
Surgical management of breast cancer in the elderly patient Baiba J. Grube, M.D., Nora M. Hansen, M.D., Wei Ye, M.S., Temple Herlong, Armando E. Giuliano, M.D.* Joyce Eisenberg Keefer Breast Center, John Wayne Cancer Institute at Saint John’s Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA Manuscript received June 29, 2001; revised manuscript July 10, 2001
Abstract Background: Breast cancer in the older woman is a major health issue and therapeutic challenge. This study asked if presentation, surgical treatment, and outcome of breast cancer are different in elderly women compared with their younger counterparts. Methods: There were 816 women ⬍70 years (younger) and 190 ⱖ70 years (older) treated surgically for breast carcinoma between January 1992 and April 2000. Data for younger and older patients was analyzed from our prospective database. Results: More older women had mammographic lesions (P ⬍0.006). Breast conservation was the treatment of choice for both groups. Stage, tumor size, histology and disease-specific survival were similar for both. There was no evidence of disease in 93% of cases in the ⬍70 years group at median follow-up of 38.4 months and 91% for the ⱖ70 years group at 44.5 months. Conclusions: In our population the presentation, surgical treatment, and survival from breast cancer is similar in older and younger women. © 2001 Excerpta Medica, Inc. All rights reserved. Keywords: Breast neoplasms; Elderly; Surgical treatment; Practice patterns; Surgical clinical trials
Breast cancer is the most common malignancy in women and the incidence increases with age. Breast cancer occurs in approximately 210 women per 100,000 between age 50 and 54, 300 per 100,000 for women over age 70, and exceeds 430 per 100,000 in women over age 80 [1]. As the incidence increases with age, the mortality rate from breast cancer also rises dramatically, doubling in 70-year-olds and tripling in 80-year-olds compared with 50-year-olds [2]. The life expectancy of elderly women in Western cultures is relatively long: if a woman reaches 70 years of age, her average life expectancy is 14 years, and it is 8.5 years if she reaches 80 years of age [3]. This is modified by the general health of the woman and can be significantly greater for healthy women. Because life expectancy is not restricted by age alone, initiating good surveillance to detect early-stage breast disease is important for local control, preven-
Presented at the Second Annual Meeting of the American Society of Breast Surgeons, La Jolla, California, May 3– 6, 2001. * Corresponding author. Tel.: ⫹1-310-829-8089; fax: ⫹1-310-9983995. E-mail address: [email protected]
tion of metastatic disease, breast preservation and quality of life [4]. Despite the high prevalence of breast cancer in the older population, the elderly have been largely excluded from clinical trials that establish state-of-the art treatment [5]. The guidelines for diagnosis and treatment of breast cancer in the older population are therefore variable [1,4 –10]. Standard treatment of early-stage breast cancer includes surgery, radiation, chemotherapy and hormonal therapy with specific recommendations based on stage of disease. These treatment recommendations are often modified in the older population due to comorbidity, functional status, shorter life expectancy, quality of life issues, psychosocial problems, economic resources, caregiver issues, and fear of morbidity and mortality from the treatment intervention [6,11]. The end result has often been lesser intervention for older patients. This has included less aggressive surgery, omission of radiation, exclusion of chemotherapy, and increased use of tamoxifen [6,7,9,10,12–16]. The purpose of this study was to determine if the presentation, surgical treatment, participation in surgical clinical trials, and outcome from breast cancer are significantly different in elderly women (ⱖ70 years) than in their younger counterparts in a single large breast cancer center.
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B.J. Grube et al. / The American Journal of Surgery 182 (2001) 359 –364
Methods The study population consisted of women treated at the Joyce Eisenberg Keefer Breast Center between January 1992 and April 2000. The data were obtained from our prospectively collected database. Information regarding diagnosis, surgical treatment, participation in surgical trials, stage of disease, histology, and survival were analyzed. Patients who did not undergo operation at our institution or presented with stage IV breast cancer were excluded. Patients with invasive carcinoma of all histologic classifications and noninvasive carcinoma including Paget’s disease were included in the analysis. Patients with lobular carcinoma in situ only, phyllodes tumors, and sarcomas were excluded. Since May of 1999, our patients have been offered participation in the ACSOG Z10 and Z11 trials and all are excluded. This study includes patients entered into our prospective trial of sentinel lymph node dissection (SLND) followed by routine axillary lymph node dissection (ALND) conducted from July 1994 through October 1995 [17]. It also includes the prospective trial of SLND alone for nodenegative patients conducted from October 1995 to July 1997 [18]. The protocol methods for those trials were in accordance with the ethical standards of the joint Saint John’s Health Center and John Wayne Cancer Institute Institutional Review Board at Santa Monica, California, and also complied with the Helsinki Declaration. Written informed consent was obtained from all study participants. Tumor staging was according to the TNM system of the American Joint Committee on Cancer (AJCC) [19]. The tumor size was measured on histopathologic sectioning. The clinical characteristics, tumor histology, and axillary status were recorded prospectively for each patient. Disease-specific survival curves were estimated by the Kaplan-Meier method. Log rank test was used to compare the survival between the two age groups. Disease-specific survival was defined as the period between the diagnosis of primary cancer to death from breast cancer. The t test was carried out to determine the differences in numerical variables between the age groups. The Pearson chi-square test was used to test the association between age and categorical characteristics. All statistical analyses were two-tailed and performed using Statistical Analysis System (SAS Institute, Inc., Cary, North Carolina). A P value of ⬍0.05 was considered significant.
Results There were 816 patients (81%) in the ⬍70-year-old group (younger) and 190 (19%) in the ⱖ70-year-old group (older) treated for carcinoma of the breast at the Joyce Eisenberg Keefer Breast Center between January 9, 1992, and April 20, 2000 (Table 1). The median age was 53 years for the younger group and 75 years for the older group. In the younger group, 20 patients had bilateral breast cancer
Table 1 Patient and case characteristics for younger and older breast cancer patients Younger group Older group Number of patients 816 Number of cases 836 Synchronous cases 11 Metachronous cases 9 Mean age (years) 52.8 Age range (years) 27 to 69 Physical examination (number of cases) Nonpalpable 364/836 (44%) Palpable mass 472/836 (56%) Surgical procedure (number of cases) Breast conservation 665/836 (80%) Mastectomy 171/836 (20%) Participation in clinical trials Sentinel node trials 655 Other trials 441
P value
190 198 2 6 76.2 70 to 96
108/198 (55%) 0.006 90/198 (45%)
169/198 (85%) 0.063 29/198 (15%) 153 99
0.748
during the study period with 11 synchronous and 9 metachronous events. In the older group, there were 8 bilateral breast cancers during the study period, 2 synchronous and 6 metachronous occurrences. One additional patient had metachronous breast cancers. The first event occurred at age 67 and the second at age 73. For statistical purposes, the first event was evaluated in the younger group and the second in the older group. The total number of patients in the study is 1,005. Tumors were discovered only by mammogram less often in the younger group than the older group (P ⬍0.006). Clinical examination identified a palpable tumor in a larger number of cases in the younger group than in the older group. There was no statistically significant difference in patient participation in surgical clinical trials for intraoperative lymphatic mapping by age group (P ⫽ 0.748). Some patients were enrolled in more than one protocol if it did not conflict with the sentinel node (SN) study. The surgical management of breast cancer with respect to patient age is shown in Table 1. Breast conservation surgery was selected by a large proportion of patients in both groups. There was no statistically significant difference in desire for breast preservation by age (P ⫽ 0.063). In the younger group, 80% of the patients underwent breast conservation surgery compared with 85% in the older group. The type of breast-conserving operation performed in the younger group compared with the older group was similar. Younger and older patients had segmentectomy alone in 7% versus 7% of the cases, segmentectomy plus ALND in 9% versus 16%, segmentectomy with SLND followed by ALND in 42% versus 38%, and segmentectomy with SLND only in 42% versus 39% of cases, respectively. Segmentectomy alone without axillary staging was performed for ductal carcinoma in situ (DCIS) only in the younger group and for DCIS in the older patients except for 3 cases of invasive
B.J. Grube et al. / The American Journal of Surgery 182 (2001) 359 –364 Table 2 AJCC stage, tumor size, and histologic distribution by patient age
AJCC stage (number of cases) Stage 0 Stage I Stage II Stage III Tumor size (mean cm) Tis T1 T2 T3 T4 Overall Tumor histology (number of cases) DCIS/Paget’s Infiltrating ductal Infiltrating lobular Other
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Table 3 Outcome by patient age
Younger group Older group P value
Status
Number of younger patients
Number of older patients
112 (13%) 344 (41%) 333 (40%) 46 (6%)
No evidence of disease Alive with disease Died Dead of disease Dead unrelated Lost to follow-up Median follow-up (months) Range of follow-up (months)
755 (93%) 26 (3%) 28 (3%) 20/28 (71%) 8/28 (29%) 7 (1%) 38.4 0.2–111
172 (91%) 3 (2%) 12 (6%) 5/12 (42%) 7/12 (58%) 3 (2%) 44.5 0.26–106
26 (13%) 97 (49%) 66 (33%) 8 (5%)
0.209
2.26 ⫾ 2.40 1.16 ⫾ 0.49 2.89 ⫾ 0.74 6.79 ⫾ 2.41 14.50 ⫾ 7.78 1.99 ⫾ 1.82
2.62 ⫾ 1.85 1.20 ⫾ 0.45 2.84 ⫾ 0.68 6.38 ⫾ 1.24 0 1.85 ⫾ 1.43
0.4803 0.4089 0.7015 0.4690
115 (14%) 616 (74%) 85 (10%) 20 (2%)
27 (14%) 136 (69%) 25 (13%) 10 (5%)
0.154
0.2997
AJCC ⫽ American Joint Committee on Cancer; DCIS ⫽ ductal carcinoma in situ.
carcinoma; 2 were tubular carcinomas and 1 was a small invasive ductal carcinoma. There were 171 cases in the younger patient group who underwent mastectomy with or without axillary staging. In this group there were 23 patients (13%) who elected to have a prophylactic contralateral mastectomy, and 74% of these women had immediate reconstruction. In the remaining 148 mastectomy cases, there were 10 occurrences of bilateral breast cancer without reconstruction. Immediate reconstruction was performed in 70 (51%) of the remaining 138 cases. In the older group, there were 29 (15%) patients who underwent mastectomy and only 2 elected to have immediate reconstruction. One older patient underwent prophylactic contralateral mastectomy. Using the current AJCC staging system for breast cancer, the distribution of stage of disease was similar for the two study groups (Table 2). One patient in each study group had neoadjuvant chemotherapy with no measurable residual tumor and could not be pathologically staged. Three cases of high-grade DCIS with comedo necrosis in the younger group and 1 case in the older group had intraoperative lymphatic mapping, and the SN was positive for each. Despite careful scrutiny of the tumor specimen, no invasive component could be identified in these cases. The tumor histology remained DCIS, but was classified as stage II disease based on the status of the SN. The majority of patients, 81% in the younger compared with 82% in the older group, presented with stage I or II disease. There was no association between age and stage (P ⫽ 0.209). There was no difference in the overall mean tumor size for the younger group compared with the older group (P ⫽ 0.2997; Table 2). The mean tumor size by tumor stage was similar for the two groups (Table 2). There were 2 patients in each group whose tumor size was not evaluable. One patient in
each group had neoadjuvant chemotherapy and a second patient in each group had multifocal DCIS. Invasive ductal carcinoma accounted for the predominant histologic type in 74% of the cases in the younger group and in 69% in the older group (Table 2). For the younger patients, the infiltrating ductal carcinoma category consisted of infiltrating ductal in 530, infiltrating ductal with extensive DCIS in 79, and infiltrating ductal with associated lobular carcinoma in 7 cases. The other category included 1 adenoid cystic, 2 adenocarcinoma, 1 apocrine, 10 tubular, 3 mucinous, 2 medullary, and 1 metaplastic case. For the older patients, the infiltrating ductal category included 122 infiltrating ductal cases, 9 infiltrating ductal with extensive DCIS, and 5 infiltrating ductal associated with infiltrating lobular carcinoma. In the other category, there were 4 tubular, 5 mucinous, and 1 metaplastic carcinomas. The clinical outcome for these two patient groups is shown in Table 3. The disease-specific survival was calculated from the first tumor diagnosis in patients who had bilateral breast cancers. The mean number of months of patient follow-up was 44.5 months for the younger group and 47.3 months for the older group. The number of patients alive with no evidence of disease is 93% for the younger group and 91% for the older group. Older patients were more likely to die of unrelated causes. There was one perioperative death in the older age group from cardiac dysfunction and mural thrombus, for an overall surgical mortality of 0.53%. This occurred in a 71-year-old woman 1 week after surgery during her postoperative outpatient clinic visit. She had sudden cardiac arrest and electromechanical dissociation. An emergency transesophageal echocardiogram was obtained and revealed profound left ventricular dysfunction and large thrombi in the right atrium suggestive of pulmonary emboli, but no embolus was identified in the right pulmonary artery. There is no significant difference in disease-specific survival by age (Fig. 1).
Comments The problem of cancer in the elderly is a vital health care issue. The current cancer burden in the elderly must be
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Fig. 1. Kaplan-Meier curve of disease-specific survival by age of patient.
assessed in the context of the anticipated demographic shift of the population in the United States that is projected to comprise one in five Americans older than 65 by year 2030 [20]. In fact, the subset of patients 80 or older represents the most rapidly expanding group of elderly people [20]. The proportion of older women exceeds that of older men and gender-specific malignancies will contribute to a larger fraction of the cancer burden in the elderly. The treatment of early-stage breast cancer in the mature woman is variable in the literature. Therapeutic approaches include complete nonsurgical management with tamoxifen alone [7,12,16], limited surgery with adjuvant tamoxifen [21], breast ablation [9,22], or optimal surgery and adjuvant treatment as dictated by the stage of disease [1]. We investigated our own surgical approach to older patients diagnosed with breast cancer and compared it with that for younger patients to determine if we or the patient had a surgical treatment bias according to age of patient and if there was a difference in outcome. We also reviewed our experience of offering patients the opportunity to participate in surgical clinical trials to determine if there was treatment selection bias by age. Approximately 20% of the patient population undergoing treatment for breast cancer at our institution are 70 years old or older. Almost half of our patients presented with mammographically identified lesions. This may reflect a better screened group of patients. The detection rate for early-stage nonpalpable breast cancer in our older population was actually slightly higher and statistically significant when compared with our own patients who were younger than 70 years. A similar rate of mammographic identification of breast cancer in the older population has been observed in several recent series [6,23], but generally screening mammography has been underutilized in older patients [9,10]. There has been controversy regarding the optimal screening recommendations for older patients. There are two potential benefits from screening mammography: (1) a reduction in breast cancer mortality from earlier diagnosis,
and (2) greater likelihood for breast-conserving surgery [23]. The current study was not designed to investigate utilization of mammographic screening in the older population and cannot determine whether mammographic screening leads to identification of smaller tumors and therefore has an impact on surgical treatment choice or survival. Our older patients, however, had a statistically significant identification of mammographic lesions when compared with our younger patients. Several randomized and prospective trials evaluating the effect of mammographic screening on breast cancer mortality for older women have shown a reduction in mortality [3,24]. The controversy on mammographic screening in the older woman has focused on its value to extend life in the face of a presumed increased risk of treatment complications from competing comorbidities. On the other hand, treatment of early-stage breast cancer can prevent the side effects of metastatic disease on overall health and quality of life [3]. The potential benefit of screening mammography in the older patient may actually exceed that for younger patients, because of the decreased breast density and increased sensitivity [6]. Our data would suggest that older patients do seek out preventative care and undergo screening mammography at a high rate. This is further confirmed by our detection of six metachronous tumors in the older patients who underwent definitive surgical treatment for their second malignancy. The majority of our patients presented with early-stage disease. It is commonly reported that older patients present with more advanced disease, but the literature is variable on this point [6,7,9,23,25]. The size of tumor by T stage was similar in the two age groups. A recent study by Busch et al [6] reported that older females were diagnosed at a later stage (P ⬍0.0001). Infiltrating ductal carcinoma, as expected, accounted for the largest percentage of tumors in both groups. This is reflected in the literature in other series [8,9]. The interesting finding in these two groups of patients is the similar incidence of DCIS. A recent study reported a lower detection of highly favorable and curable preinvasive lesions in patients older than 65 years of age (9% versus 15%, P ⫽ 0.001) [10]. Surgical management followed National Institutes of Health consensus guidelines recommending breast conservation surgery with ALND for stage I and II disease. Historical studies have shown a high use of mastectomy in older patients [6,9,22,26]. Breast-conserving surgery has been used restrictively in older patients, but appears to be changing. One recent study reported that screening mammography for women older than 65 years enabled 79% of them to be eligible for breast-conserving treatment compared with those who had not undergone screening (P ⫽ 0.0044). In addition, when given the choice 70% of those women underwent breast conservation over mastectomy (P ⫽ 0.0077) [23]. In the current study, 85% of our older patients had breast conservation compared with 80% of our younger patients (P ⫽ 0.063). The percentage of women
B.J. Grube et al. / The American Journal of Surgery 182 (2001) 359 –364
undergoing axillary node dissection is reported to decrease with age [16,27,28]. Our older population with invasive carcinoma had axillary staging either by ALND or SLND. Sentinel lymphadenectomy has improved axillary staging [29] and reduced morbidity associated with ALND [18]. This is a particularly useful methodology for older patients who may have significant arthritis, degenerative joint problems, and cardiovascular compromise. Younger and older patients could participate in the sentinel node trials for axillary staging. Both age groups enrolled in these with equal frequency. The assumption that older patients have serious concurrent medical problems precluding standard surgical intervention has not been born out in the literature or our study. Previously quoted surgical mortality rates for older patients have been 1.5% to 2.9% [6,9], which are slightly higher than the current study of 0.52%. As these have all been nonrandomized studies, they may reflect selection bias. Life expectancy for women over age 70 is 14 years; over age 80, it is 8.5 years [3]. In our patients, more than 90% of patients in both age groups had no evidence of disease at a median follow-up of 38.4 months for younger patients and 44.5 months for older patients. These are encouraging findings and can be of value when discussing surgical treatment options with those in the later decades of their lives. The observations in this study suggest that breast health surveillance programs should be performed to identify early-stage breast cancer in older patients. When breast cancer is diagnosed at an early stage and treated with standard surgical treatment there is a low mortality rate with a comparable survival to that of younger patients. Some suggest that physicians may be making judgments about absolute benefit of staging and adjuvant therapies according to chronological age only, without regard to physiological status, which may or may not be correct [26,30]. Prospective randomized trials are critical to determine what type of screening, surveillance, surgery and adjuvant treatment is best suited for the older population. Participation in trials should help answer some of these questions in the future and ensure that all women, irrespective of age, are afforded the best care possible. In our institution a nurse-physician team is used to explain alternative treatments and inform patients of options in an unhurried manner. Data from this single institution study suggest that older patients are interested in novel treatments and are willing to enroll in prospective clinical trials. Our data support the conclusion that our surgical approach is similar irrespective of age and the resultant outcomes are comparable for younger and older women. References [1] Ashkanani F, Eremin O, Heys SD. The management of cancer of the breast in the elderly. Eur J Surg Oncol 1998;24:396 – 402. [2] Caplan LS. Disparities in breast cancer screening: is it ethical? Pub Health Rev 1997;25:31– 41.
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[3] van Dijck JAAM, Broeders MJM, Verbeek ALM. Mammographic screening in older women. Drugs Aging 1997;10:69 –79. [4] Cerrotta A, Lozza L, Kenda R, et al. Current controversies in the therapeutic approach to early breast cancer in the elderly. Rays 1997;22(suppl 1):66 – 8. [5] Law TM, Hesketh PJ, Porter KA, et al. Breast cancer in elderly women. Surg Clin North Am 1996;76:289 –308. [6] Busch E, Kemeny M, Fremgen A, et al. Patterns of breast cancer care in the elderly. Cancer 1996;78:101–11. [7] Bergman L, Dekker G, van Leeuwen FE, et al. The effect of age on treatment choice and survival in elderly breast cancer patients. Cancer 1991;67:2227–34. [8] Berg JW, Hutter RVP. Breast cancer. Cancer 1994;75:257– 69. [9] Singletary SE, Shallenberger R, Guinee VF. Breast cancer in the elderly. Ann Surg 1993;218:667–71. [10] Wanebo HJ, Cole B, Chung M, et al. Is surgical management compromised in elderly patients with breast cancer? Ann Surg 1997;225: 579 – 89. [11] Yancik R, Ganz PA, Varricchio CG, Conley B. Perspectives on comorbidity and cancer in older patients: approaches to expand the knowledge base. J Clin Oncol 2001;19:1147–51. [12] Robertson JFR, Ellis IO, Elston CW, Blamey RW. Mastectomy or tamoxifen as initial therapy for operable breast cancer in elderly patients: 5-year follow-up. Eur J Cancer 1992;28A:908 –10. [13] Gazet JC, Ford HT, Bland JM, et al. Prospective randomized trial of tamoxifen versus surgery in elderly patients with breast cancer. Lancet 1988;1:679 – 81. [14] Bates T, Riley DL, Fallowfield L, Baum M. Breast cancer in elderly women: a Cancer Research Campaign trial comparing treatment with tamoxifen and optimal surgery with tamoxifen alone. Br J Surg 1991;78:591– 4. [15] Susann P, Susann PW, Ackerman S, et al. Treatment outcomes for female octogenarians with breast cancer. Am Surg 1999;65:399 – 401. [16] Al-Hilay M, Willsher PC, Robertson JFR, Blamey RW. Audit of a conservative management policy of the axilla in elderly patients with operable breast cancer. Eur J Surg Oncol 1997;23:339 – 40. [17] Giuliano AE, Jones RC, Brennan M, Statman R. Sentinel lymphadenectomy in breast cancer. J Clin Oncol 1997;15:2345–50. [18] Giuliano AE, Haigh PI, Brennan MB, et al. Prospective observational study of sentinel lymphadenectomy without further axillary dissection in patients with sentinel node-negative breast cancer. J Clin Oncol 2000;18:2553–9. [19] Fleming ID, Cooper JS, Henson DE, et al, editors. AJCC cancer staging handbook. 5th ed. Philadelphia: Lippincott-Raven, 1998. [20] Yancik R. State of the art: epidemiology of cancer in the elderly, current status and projections for the future. Rays 1997;22(suppl 1):3–9. [21] Yeh S, Tan LR, O’Connell TX. Segmental mastectomy and tamoxifen alone provide adequate locoregional control of breast cancer in elderly women. Am Surg 1997;63:854 –7. [22] Kessler HJ, Seton JZ. The treatment of operable breast cancer in the elderly female. Am J Surg 1978;135:664 – 6. [23] Solin LJ, Schultz DJ, Hanchak NA, Kessler HB. Patterns of treatment for older women with newly diagnosed breast carcinoma. Am J Clin Oncol 1999;22:107–13. [24] Tabar L, Fagerberg G, Duffy SNW, Day NE. The Swedish two county trial of mammographic screening for breast cancer: recent results and calculation of benefit. J Epidemiol Commun Health 1989;43:107–14. [25] Hunt KE, Fry D, Bland K. Breast carcinoma in the elderly patient. Am J Surg 1990;140:339 – 42. [26] Hillner BE, Penberthy L, Desch CE, et al. Variation in staging and treatment of local and regional breast cancer in the elderly. Breast Cancer Res Treat 1996;40:75– 86. [27] Bland KI, Scott-Conner CEH, Menck H, Winchester DP. Axillary dissection in breast-conserving surgery for stage I and II breast
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cancer: a national cancer data base study of patterns of omission and implications for survival. J Am Coll Surg 1999;188:586 –96. [28] Du X, Freeman JL, Goodwin JS. The declining use of axillary dissection in patients with early stage breast cancer. Breast Cancer Res Treat 1999;53:137– 44.
[29] Giuliano AE, Dale, PS, Turner, RR, et al. Improved axillary staging of breast cancer with sentinel lymphadenectomy. Ann Surg 1995;222: 394 – 401. [30] Greenfield S, Blanco DM, Elashoff RM, Ganz PA. Patterns of care related to age of breast cancer patients. JAMA 1987;257:2766 –70.
Surgical management of breast cancer in the elderly patient Baiba J. Grube, M.D., Nora M. Hansen, M.D., Wei Ye, M.S., Temple Herlong, Armando E. Giuliano, M.D.* Joyce Eisenberg Keefer Breast Center, John Wayne Cancer Institute at Saint John’s Health Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404, USA Manuscript received June 29, 2001; revised manuscript July 10, 2001
Abstract Background: Breast cancer in the older woman is a major health issue and therapeutic challenge. This study asked if presentation, surgical treatment, and outcome of breast cancer are different in elderly women compared with their younger counterparts. Methods: There were 816 women ⬍70 years (younger) and 190 ⱖ70 years (older) treated surgically for breast carcinoma between January 1992 and April 2000. Data for younger and older patients was analyzed from our prospective database. Results: More older women had mammographic lesions (P ⬍0.006). Breast conservation was the treatment of choice for both groups. Stage, tumor size, histology and disease-specific survival were similar for both. There was no evidence of disease in 93% of cases in the ⬍70 years group at median follow-up of 38.4 months and 91% for the ⱖ70 years group at 44.5 months. Conclusions: In our population the presentation, surgical treatment, and survival from breast cancer is similar in older and younger women. © 2001 Excerpta Medica, Inc. All rights reserved. Keywords: Breast neoplasms; Elderly; Surgical treatment; Practice patterns; Surgical clinical trials
Breast cancer is the most common malignancy in women and the incidence increases with age. Breast cancer occurs in approximately 210 women per 100,000 between age 50 and 54, 300 per 100,000 for women over age 70, and exceeds 430 per 100,000 in women over age 80 [1]. As the incidence increases with age, the mortality rate from breast cancer also rises dramatically, doubling in 70-year-olds and tripling in 80-year-olds compared with 50-year-olds [2]. The life expectancy of elderly women in Western cultures is relatively long: if a woman reaches 70 years of age, her average life expectancy is 14 years, and it is 8.5 years if she reaches 80 years of age [3]. This is modified by the general health of the woman and can be significantly greater for healthy women. Because life expectancy is not restricted by age alone, initiating good surveillance to detect early-stage breast disease is important for local control, preven-
Presented at the Second Annual Meeting of the American Society of Breast Surgeons, La Jolla, California, May 3– 6, 2001. * Corresponding author. Tel.: ⫹1-310-829-8089; fax: ⫹1-310-9983995. E-mail address: [email protected]
tion of metastatic disease, breast preservation and quality of life [4]. Despite the high prevalence of breast cancer in the older population, the elderly have been largely excluded from clinical trials that establish state-of-the art treatment [5]. The guidelines for diagnosis and treatment of breast cancer in the older population are therefore variable [1,4 –10]. Standard treatment of early-stage breast cancer includes surgery, radiation, chemotherapy and hormonal therapy with specific recommendations based on stage of disease. These treatment recommendations are often modified in the older population due to comorbidity, functional status, shorter life expectancy, quality of life issues, psychosocial problems, economic resources, caregiver issues, and fear of morbidity and mortality from the treatment intervention [6,11]. The end result has often been lesser intervention for older patients. This has included less aggressive surgery, omission of radiation, exclusion of chemotherapy, and increased use of tamoxifen [6,7,9,10,12–16]. The purpose of this study was to determine if the presentation, surgical treatment, participation in surgical clinical trials, and outcome from breast cancer are significantly different in elderly women (ⱖ70 years) than in their younger counterparts in a single large breast cancer center.
0002-9610/01/$ – see front matter © 2001 Excerpta Medica, Inc. All rights reserved. PII: S 0 0 0 2 - 9 6 1 0 ( 0 1 ) 0 0 7 3 7 - 1
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B.J. Grube et al. / The American Journal of Surgery 182 (2001) 359 –364
Methods The study population consisted of women treated at the Joyce Eisenberg Keefer Breast Center between January 1992 and April 2000. The data were obtained from our prospectively collected database. Information regarding diagnosis, surgical treatment, participation in surgical trials, stage of disease, histology, and survival were analyzed. Patients who did not undergo operation at our institution or presented with stage IV breast cancer were excluded. Patients with invasive carcinoma of all histologic classifications and noninvasive carcinoma including Paget’s disease were included in the analysis. Patients with lobular carcinoma in situ only, phyllodes tumors, and sarcomas were excluded. Since May of 1999, our patients have been offered participation in the ACSOG Z10 and Z11 trials and all are excluded. This study includes patients entered into our prospective trial of sentinel lymph node dissection (SLND) followed by routine axillary lymph node dissection (ALND) conducted from July 1994 through October 1995 [17]. It also includes the prospective trial of SLND alone for nodenegative patients conducted from October 1995 to July 1997 [18]. The protocol methods for those trials were in accordance with the ethical standards of the joint Saint John’s Health Center and John Wayne Cancer Institute Institutional Review Board at Santa Monica, California, and also complied with the Helsinki Declaration. Written informed consent was obtained from all study participants. Tumor staging was according to the TNM system of the American Joint Committee on Cancer (AJCC) [19]. The tumor size was measured on histopathologic sectioning. The clinical characteristics, tumor histology, and axillary status were recorded prospectively for each patient. Disease-specific survival curves were estimated by the Kaplan-Meier method. Log rank test was used to compare the survival between the two age groups. Disease-specific survival was defined as the period between the diagnosis of primary cancer to death from breast cancer. The t test was carried out to determine the differences in numerical variables between the age groups. The Pearson chi-square test was used to test the association between age and categorical characteristics. All statistical analyses were two-tailed and performed using Statistical Analysis System (SAS Institute, Inc., Cary, North Carolina). A P value of ⬍0.05 was considered significant.
Results There were 816 patients (81%) in the ⬍70-year-old group (younger) and 190 (19%) in the ⱖ70-year-old group (older) treated for carcinoma of the breast at the Joyce Eisenberg Keefer Breast Center between January 9, 1992, and April 20, 2000 (Table 1). The median age was 53 years for the younger group and 75 years for the older group. In the younger group, 20 patients had bilateral breast cancer
Table 1 Patient and case characteristics for younger and older breast cancer patients Younger group Older group Number of patients 816 Number of cases 836 Synchronous cases 11 Metachronous cases 9 Mean age (years) 52.8 Age range (years) 27 to 69 Physical examination (number of cases) Nonpalpable 364/836 (44%) Palpable mass 472/836 (56%) Surgical procedure (number of cases) Breast conservation 665/836 (80%) Mastectomy 171/836 (20%) Participation in clinical trials Sentinel node trials 655 Other trials 441
P value
190 198 2 6 76.2 70 to 96
108/198 (55%) 0.006 90/198 (45%)
169/198 (85%) 0.063 29/198 (15%) 153 99
0.748
during the study period with 11 synchronous and 9 metachronous events. In the older group, there were 8 bilateral breast cancers during the study period, 2 synchronous and 6 metachronous occurrences. One additional patient had metachronous breast cancers. The first event occurred at age 67 and the second at age 73. For statistical purposes, the first event was evaluated in the younger group and the second in the older group. The total number of patients in the study is 1,005. Tumors were discovered only by mammogram less often in the younger group than the older group (P ⬍0.006). Clinical examination identified a palpable tumor in a larger number of cases in the younger group than in the older group. There was no statistically significant difference in patient participation in surgical clinical trials for intraoperative lymphatic mapping by age group (P ⫽ 0.748). Some patients were enrolled in more than one protocol if it did not conflict with the sentinel node (SN) study. The surgical management of breast cancer with respect to patient age is shown in Table 1. Breast conservation surgery was selected by a large proportion of patients in both groups. There was no statistically significant difference in desire for breast preservation by age (P ⫽ 0.063). In the younger group, 80% of the patients underwent breast conservation surgery compared with 85% in the older group. The type of breast-conserving operation performed in the younger group compared with the older group was similar. Younger and older patients had segmentectomy alone in 7% versus 7% of the cases, segmentectomy plus ALND in 9% versus 16%, segmentectomy with SLND followed by ALND in 42% versus 38%, and segmentectomy with SLND only in 42% versus 39% of cases, respectively. Segmentectomy alone without axillary staging was performed for ductal carcinoma in situ (DCIS) only in the younger group and for DCIS in the older patients except for 3 cases of invasive
B.J. Grube et al. / The American Journal of Surgery 182 (2001) 359 –364 Table 2 AJCC stage, tumor size, and histologic distribution by patient age
AJCC stage (number of cases) Stage 0 Stage I Stage II Stage III Tumor size (mean cm) Tis T1 T2 T3 T4 Overall Tumor histology (number of cases) DCIS/Paget’s Infiltrating ductal Infiltrating lobular Other
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Table 3 Outcome by patient age
Younger group Older group P value
Status
Number of younger patients
Number of older patients
112 (13%) 344 (41%) 333 (40%) 46 (6%)
No evidence of disease Alive with disease Died Dead of disease Dead unrelated Lost to follow-up Median follow-up (months) Range of follow-up (months)
755 (93%) 26 (3%) 28 (3%) 20/28 (71%) 8/28 (29%) 7 (1%) 38.4 0.2–111
172 (91%) 3 (2%) 12 (6%) 5/12 (42%) 7/12 (58%) 3 (2%) 44.5 0.26–106
26 (13%) 97 (49%) 66 (33%) 8 (5%)
0.209
2.26 ⫾ 2.40 1.16 ⫾ 0.49 2.89 ⫾ 0.74 6.79 ⫾ 2.41 14.50 ⫾ 7.78 1.99 ⫾ 1.82
2.62 ⫾ 1.85 1.20 ⫾ 0.45 2.84 ⫾ 0.68 6.38 ⫾ 1.24 0 1.85 ⫾ 1.43
0.4803 0.4089 0.7015 0.4690
115 (14%) 616 (74%) 85 (10%) 20 (2%)
27 (14%) 136 (69%) 25 (13%) 10 (5%)
0.154
0.2997
AJCC ⫽ American Joint Committee on Cancer; DCIS ⫽ ductal carcinoma in situ.
carcinoma; 2 were tubular carcinomas and 1 was a small invasive ductal carcinoma. There were 171 cases in the younger patient group who underwent mastectomy with or without axillary staging. In this group there were 23 patients (13%) who elected to have a prophylactic contralateral mastectomy, and 74% of these women had immediate reconstruction. In the remaining 148 mastectomy cases, there were 10 occurrences of bilateral breast cancer without reconstruction. Immediate reconstruction was performed in 70 (51%) of the remaining 138 cases. In the older group, there were 29 (15%) patients who underwent mastectomy and only 2 elected to have immediate reconstruction. One older patient underwent prophylactic contralateral mastectomy. Using the current AJCC staging system for breast cancer, the distribution of stage of disease was similar for the two study groups (Table 2). One patient in each study group had neoadjuvant chemotherapy with no measurable residual tumor and could not be pathologically staged. Three cases of high-grade DCIS with comedo necrosis in the younger group and 1 case in the older group had intraoperative lymphatic mapping, and the SN was positive for each. Despite careful scrutiny of the tumor specimen, no invasive component could be identified in these cases. The tumor histology remained DCIS, but was classified as stage II disease based on the status of the SN. The majority of patients, 81% in the younger compared with 82% in the older group, presented with stage I or II disease. There was no association between age and stage (P ⫽ 0.209). There was no difference in the overall mean tumor size for the younger group compared with the older group (P ⫽ 0.2997; Table 2). The mean tumor size by tumor stage was similar for the two groups (Table 2). There were 2 patients in each group whose tumor size was not evaluable. One patient in
each group had neoadjuvant chemotherapy and a second patient in each group had multifocal DCIS. Invasive ductal carcinoma accounted for the predominant histologic type in 74% of the cases in the younger group and in 69% in the older group (Table 2). For the younger patients, the infiltrating ductal carcinoma category consisted of infiltrating ductal in 530, infiltrating ductal with extensive DCIS in 79, and infiltrating ductal with associated lobular carcinoma in 7 cases. The other category included 1 adenoid cystic, 2 adenocarcinoma, 1 apocrine, 10 tubular, 3 mucinous, 2 medullary, and 1 metaplastic case. For the older patients, the infiltrating ductal category included 122 infiltrating ductal cases, 9 infiltrating ductal with extensive DCIS, and 5 infiltrating ductal associated with infiltrating lobular carcinoma. In the other category, there were 4 tubular, 5 mucinous, and 1 metaplastic carcinomas. The clinical outcome for these two patient groups is shown in Table 3. The disease-specific survival was calculated from the first tumor diagnosis in patients who had bilateral breast cancers. The mean number of months of patient follow-up was 44.5 months for the younger group and 47.3 months for the older group. The number of patients alive with no evidence of disease is 93% for the younger group and 91% for the older group. Older patients were more likely to die of unrelated causes. There was one perioperative death in the older age group from cardiac dysfunction and mural thrombus, for an overall surgical mortality of 0.53%. This occurred in a 71-year-old woman 1 week after surgery during her postoperative outpatient clinic visit. She had sudden cardiac arrest and electromechanical dissociation. An emergency transesophageal echocardiogram was obtained and revealed profound left ventricular dysfunction and large thrombi in the right atrium suggestive of pulmonary emboli, but no embolus was identified in the right pulmonary artery. There is no significant difference in disease-specific survival by age (Fig. 1).
Comments The problem of cancer in the elderly is a vital health care issue. The current cancer burden in the elderly must be
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Fig. 1. Kaplan-Meier curve of disease-specific survival by age of patient.
assessed in the context of the anticipated demographic shift of the population in the United States that is projected to comprise one in five Americans older than 65 by year 2030 [20]. In fact, the subset of patients 80 or older represents the most rapidly expanding group of elderly people [20]. The proportion of older women exceeds that of older men and gender-specific malignancies will contribute to a larger fraction of the cancer burden in the elderly. The treatment of early-stage breast cancer in the mature woman is variable in the literature. Therapeutic approaches include complete nonsurgical management with tamoxifen alone [7,12,16], limited surgery with adjuvant tamoxifen [21], breast ablation [9,22], or optimal surgery and adjuvant treatment as dictated by the stage of disease [1]. We investigated our own surgical approach to older patients diagnosed with breast cancer and compared it with that for younger patients to determine if we or the patient had a surgical treatment bias according to age of patient and if there was a difference in outcome. We also reviewed our experience of offering patients the opportunity to participate in surgical clinical trials to determine if there was treatment selection bias by age. Approximately 20% of the patient population undergoing treatment for breast cancer at our institution are 70 years old or older. Almost half of our patients presented with mammographically identified lesions. This may reflect a better screened group of patients. The detection rate for early-stage nonpalpable breast cancer in our older population was actually slightly higher and statistically significant when compared with our own patients who were younger than 70 years. A similar rate of mammographic identification of breast cancer in the older population has been observed in several recent series [6,23], but generally screening mammography has been underutilized in older patients [9,10]. There has been controversy regarding the optimal screening recommendations for older patients. There are two potential benefits from screening mammography: (1) a reduction in breast cancer mortality from earlier diagnosis,
and (2) greater likelihood for breast-conserving surgery [23]. The current study was not designed to investigate utilization of mammographic screening in the older population and cannot determine whether mammographic screening leads to identification of smaller tumors and therefore has an impact on surgical treatment choice or survival. Our older patients, however, had a statistically significant identification of mammographic lesions when compared with our younger patients. Several randomized and prospective trials evaluating the effect of mammographic screening on breast cancer mortality for older women have shown a reduction in mortality [3,24]. The controversy on mammographic screening in the older woman has focused on its value to extend life in the face of a presumed increased risk of treatment complications from competing comorbidities. On the other hand, treatment of early-stage breast cancer can prevent the side effects of metastatic disease on overall health and quality of life [3]. The potential benefit of screening mammography in the older patient may actually exceed that for younger patients, because of the decreased breast density and increased sensitivity [6]. Our data would suggest that older patients do seek out preventative care and undergo screening mammography at a high rate. This is further confirmed by our detection of six metachronous tumors in the older patients who underwent definitive surgical treatment for their second malignancy. The majority of our patients presented with early-stage disease. It is commonly reported that older patients present with more advanced disease, but the literature is variable on this point [6,7,9,23,25]. The size of tumor by T stage was similar in the two age groups. A recent study by Busch et al [6] reported that older females were diagnosed at a later stage (P ⬍0.0001). Infiltrating ductal carcinoma, as expected, accounted for the largest percentage of tumors in both groups. This is reflected in the literature in other series [8,9]. The interesting finding in these two groups of patients is the similar incidence of DCIS. A recent study reported a lower detection of highly favorable and curable preinvasive lesions in patients older than 65 years of age (9% versus 15%, P ⫽ 0.001) [10]. Surgical management followed National Institutes of Health consensus guidelines recommending breast conservation surgery with ALND for stage I and II disease. Historical studies have shown a high use of mastectomy in older patients [6,9,22,26]. Breast-conserving surgery has been used restrictively in older patients, but appears to be changing. One recent study reported that screening mammography for women older than 65 years enabled 79% of them to be eligible for breast-conserving treatment compared with those who had not undergone screening (P ⫽ 0.0044). In addition, when given the choice 70% of those women underwent breast conservation over mastectomy (P ⫽ 0.0077) [23]. In the current study, 85% of our older patients had breast conservation compared with 80% of our younger patients (P ⫽ 0.063). The percentage of women
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undergoing axillary node dissection is reported to decrease with age [16,27,28]. Our older population with invasive carcinoma had axillary staging either by ALND or SLND. Sentinel lymphadenectomy has improved axillary staging [29] and reduced morbidity associated with ALND [18]. This is a particularly useful methodology for older patients who may have significant arthritis, degenerative joint problems, and cardiovascular compromise. Younger and older patients could participate in the sentinel node trials for axillary staging. Both age groups enrolled in these with equal frequency. The assumption that older patients have serious concurrent medical problems precluding standard surgical intervention has not been born out in the literature or our study. Previously quoted surgical mortality rates for older patients have been 1.5% to 2.9% [6,9], which are slightly higher than the current study of 0.52%. As these have all been nonrandomized studies, they may reflect selection bias. Life expectancy for women over age 70 is 14 years; over age 80, it is 8.5 years [3]. In our patients, more than 90% of patients in both age groups had no evidence of disease at a median follow-up of 38.4 months for younger patients and 44.5 months for older patients. These are encouraging findings and can be of value when discussing surgical treatment options with those in the later decades of their lives. The observations in this study suggest that breast health surveillance programs should be performed to identify early-stage breast cancer in older patients. When breast cancer is diagnosed at an early stage and treated with standard surgical treatment there is a low mortality rate with a comparable survival to that of younger patients. Some suggest that physicians may be making judgments about absolute benefit of staging and adjuvant therapies according to chronological age only, without regard to physiological status, which may or may not be correct [26,30]. Prospective randomized trials are critical to determine what type of screening, surveillance, surgery and adjuvant treatment is best suited for the older population. Participation in trials should help answer some of these questions in the future and ensure that all women, irrespective of age, are afforded the best care possible. In our institution a nurse-physician team is used to explain alternative treatments and inform patients of options in an unhurried manner. Data from this single institution study suggest that older patients are interested in novel treatments and are willing to enroll in prospective clinical trials. Our data support the conclusion that our surgical approach is similar irrespective of age and the resultant outcomes are comparable for younger and older women. References [1] Ashkanani F, Eremin O, Heys SD. The management of cancer of the breast in the elderly. Eur J Surg Oncol 1998;24:396 – 402. [2] Caplan LS. Disparities in breast cancer screening: is it ethical? Pub Health Rev 1997;25:31– 41.
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