Breast Cancer Treatment In Older Women

Surg Oncol Clin N Am 14 (2005) 85–102

Breast cancer treatment in older women Marissa Howard-McNatt, MDa, Kevin S. Hughes, MDa,*, Lauren A. Schnaper, MDb, Julie L. Jones, MDa, Michele Gadd, MDa, Barbara L. Smith, MD, PhDa a

Division of Surgical Oncology, Massachusetts General Hospital, 100 Blossom Street, Cox 626, Boston, MA 02114, USA b Greater Baltimore Medical Center Comprehensive Breast Care Center, Greater Baltimore Medical Center, 6701 North Charles Street, Suite 5105, Baltimore, MD 21204, USA

Breast cancer is a substantial problem in elderly women. It was reported that 30% of all breast cancers occur in women who are older than 70 years of age and 48% occur in women who are older than 65 years of age [1]. As the baby boom population ages and the health of older women improves, the number of women who are older than 65 is predicted to nearly double by 2050. In 1997, the life expectancy was 79.9 years for white women and 74.7 years for black women. The life expectancy for both races from 2001 is shown in Table 1. In 2025, the projected life expectancy is 84.8 years and 82.7 years for white and black women, respectively [2]. This will increase markedly the percentage of breast cancers that occur in this age group. This article discusses the treatment of breast cancer in the elderly and whether disparities exist in their treatment, quality of life, and survival when compared with their younger counterpart. In treating older women, it is important to understand the biology of the disease, the impact that comorbidities have on survival, and the psychosocial status of the patient. In general, breast cancer in the elderly is less aggressive and life expectancy is shorter than in the younger patient. Life expectancy in older patients can still be substantial—16 years for a 70-year-old and more than 6 years for a healthy 80-year-old [3]. The goal of treatment in older patients is control of disease for a finite lifetime rather than the expectation of cure, as in younger patients who can anticipate decades of life.

* Corresponding author. E-mail address: [email protected] (K.S. Hughes). 1055-3207/05/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/j.soc.2004.07.006

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Table 1 Average remaining lifetime at various ages according to race, preliminary data from 2001 Life expectancy Age (y)

White women (y)

Black women (y)

60 65 70 75 80 85 90

23.5 19.5 15.7 12.3 9.3 6.7 4.8

21.5 17.9 14.7 11.8 9.2 7.0 5.3

Data from National Vital Statistics Reports 2003;51(5):25.

Yancik et al [4] found that elderly women have equivalent survival when compared with younger women in terms of localized disease; however, comorbid disease plays a significant role with regard to actual survival. In 1994, Satariano et al [5] reported that mortality in women who were aged 40 to 54 years at the time of diagnosis was nearly six times more likely to be attributable to breast cancer than to some other cause. In contrast, mortality in women who were aged 75 to 84 years at diagnosis was attributable to breast cancer in fewer than 50% of cases. Overall survival was related directly to the presence of comorbid conditions (eg, heart disease, diabetes, other cancers, respiratory illnesses) and was related inversely to patient age. There was a 20fold increase in nonbreast cancer deaths in patients who had three or more comorbid conditions. Furthermore, comorbidity may limit the choice of therapy. For example, congestive heart failure, which is more common in the elderly, may limit or preclude the use of doxorubicin-based chemotherapy. The number of comorbid conditions of the elderly will decline in the future as a result of better health care and healthy living. These factors will expand treatment options for the elderly. If warranted by disease presentation, healthier, older women will be candidates for more aggressive breast cancer therapy. Older survivors of breast cancer who continue to see oncologists after treatment tend to receive better secondary prevention and general medical care than those who do not; this promotes a healthier, longer survival [6] Thus, in discussing the care of the elderly, physiologic, rather than chronologic, age must be considered.

Patterns of care Despite the fact that one third of breast cancer occurs in women who are older than 70, until recently, they have been excluded from clinical trials [7]. Because there is no database treatment recommendations that specifically are for the elderly, clinicians are free to individualize care plans based on extrapolated data and experience. This led to accusations of overtreatment

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and undertreatment of older women who had breast cancer. In the past, more women were treated primarily with mastectomy [8]—possible overtreatment. Of those who received breast-conserving surgery, many did not undergo axillary dissection and were not followed by radiation therapy— possible under treatment [8–10]. Mandelblatt et al [11], in studying patterns of treatment in the elderly, found that age was a strong determinant of treatment; this confirmed the existence of age bias among physicians. They also noted that patient preferences influenced treatment choices. It has long been known that care patterns vary with geographic location and hospital characteristics. As with other patients who have breast cancer, older women are more likely to receive breast-conserving treatment at large urban hospitals or teaching hospitals that have radiation therapy centers and support services for the elderly [12]. Velanovich et al [13] pointed out that current local and national databases that are used to assess outcomes do not reflect the complexity of issues that are involved when making treatment recommendations to older women. Information regarding other illnesses and psychosocial influences are not recorded routinely. Although it is well-documented that older women receive less therapy, it is not clear whether this has a negative impact on survival. Because of the dearth of randomized trials or standardized outcomes research, lesser care has not been established as detrimental. Although observational studies linked higher rates of recurrence and decreased survival to undertreatment [14], Gajdos and coauthors [15] retrospectively studied undertreatment and standard therapy in elderly patients who had breast cancer and found no differences in survival.

Biology Breast cancer in the elderly seems to be less aggressive. Older women tend to have more estrogen receptor–positive tumors [16], whereas S-phase [17], grade [18], and p53 and HER2/neu expression [17] are decreased. Older women tend to have more lobular, mucinous, and papillary cancers than their younger counterparts [17]. A recent prospective review of 919 patients who had T1a and T1b tumors identified three factors as independent predictors of axillary nodal metastases—increasing tumor size (0.1-cm gradients), poor histologic grade, and younger age [19]. The literature contains conflicting data about the stage at which older and younger patients present. For example, Barchelli and Balzi [20] found that in patients who were younger than 39 years old, 59% had nodal involvement compared with 22% of patients who were older than 80; however, 43% of the older women did not have pathologic staging of the axilla. The total number of cases of localized disease that were reported in

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the Surveillance Epidemiology and End Results program (SEER) database from 1992 to 1999 showed that 56% of the cases were in women who were younger than 50 years of age, whereas 66% of the cases were in older women. Furthermore, regional spread is more common in younger patients (37%) than in women who are older than 50 (26%) [21]. No clear conclusion can be drawn about staging in the elderly population. Psychosocial factors Younger and older women regard a diagnosis of breast cancer differently. Breast cancer may be only one of several illnesses in an older patient, whereas it is more likely to be the only, or one of a few, diseases in a young woman. As women age, many become more frightened of deteriorating physical abilities and of dependence on others than of dying. Overall, elderly patients tend to cope better psychologically with the initial diagnosis of breast cancer [22,23]. Ganz et al [22] used interview methods to study quality-of-life issues longitudinally after their breast cancer treatment in 691 women who were older than 65 years of age. They noted a decline in the functioning levels that began in the 3 months posttreatment and lasted for the 15 months of the study. Specifically, at 3 months postoperatively they observed a significant deterioration in self-reported physical functioning that was associated with the number of comorbid conditions and chemotherapy but with no other cancer-specific treatments. In the year after breast cancer surgery, specific breast cancer treatments (mastectomy versus breast conservation, chemotherapy, or tamoxifen) were not associated with differences in the quality of life [24]. Psychologic adjustment also can be predicted by the existence of multiple life stressors before diagnosis, including loss of a child or spouse or other major life changes [25]. Young women are more likely to explore numerous sources to inform themselves about the nature of breast cancer and treatment options. They seek advice from physicians, but they also tend to use such tools as the Internet—be it good or bad—to gather additional, and sometimes, confusing, information. Older patients tend to rely on the advice of their physicians. Petrisek and his colleagues [26] found that the elderly are less likely to want to be involved in decision-making about treatment options and are less likely to seek second opinions. Other studies showed that physicians tend to spend more time with, and provide more information to, younger patients [27,28]. Maly et al [29], in a study that involved retrospective patient reporting, found that older women who had breast cancer received much less informational support than their younger counterparts, although their informational requirements were seen as similar. Some older women may find it difficult to understand the complexities of the disease and the treatment options. The physician must lend a more sympathetic ear to these individuals and patiently explain all aspects of the disease, prognosis, and

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treatment options. It is unclear whether the apparent age-related differences in patient participation in the decision process are due to generational differences, physician bias, or decreased ability to process information. Perhaps as baby boomers mature, they will continue to be more informed consumers then were previous generations. A sense of autonomy and good cosmetic outcome are probably as important to older women as they are to the younger patient. One study found that most women who were older than 70 years of age wanted breast conservation therapy and were prepared to go through radiation treatments, if needed, to preserve their breasts [30]. In dealing with the elderly, it is vital to consider quality of life. These issues include independent living, social support, ability to perform activities of daily living, religious commitments, transportation, and attitudes concerning death. Such concerns strongly influence the patient’s treatment choices and their ability to follow through with the demands of therapy. Screening The risk of developing breast cancer increases with age; therefore, older women benefit from breast cancer screening, including mammograms, clinical breast examination, and breast self-examinations. A large metaanalysis of screening mammography showed that routine annual or biennial mammography in women who were age 50 to 75 years was associated with a reduction in breast cancer–related mortality of 25% to 30% within 5 to 6 years of initiation [31]. Mammograms in the older population tend to be easier to read because of the involution of breast tissue and increase in the fat content. In addition, the longer doubling time of cancer in older women increases the window of opportunity for detecting cancer at an earlier stage. Faulk and his colleagues [32] compared mammographic results of women who were aged 50 to 64 years (n = 21,226) with those who were aged 65 years and older (n = 10,914). They found that mammography had a higher predictive value, a higher yield of positive biopsies, and a greater cancer detection rate per 1000 studies in older women. Despite the usefulness of imaging in older women, many do not obtain annual mammograms. Van Harrison and colleagues [33] reviewed mammography use rates in older women who were covered by Medicare over a 5-year period between 1993 and 1997. In their sample of 10,000 women, 43% did not have a mammogram at all, whereas the other 57% only had a mean of 2.8 mammograms during the 5-year study period. How long should elderly patients continue to receive mammograms? There is no proof that screening improves survival in women who are older than 75; however, women should be screened based on their functional status and biologic age. Some experts recommend mammography for healthy women up to the age of 85 years [34]. Mandelblatt and colleagues [35] found that the benefits of screening mammography outweighed the

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financial costs for older women, irrespective of age; however, the magnitude of benefit decreased with increasing age and increasing comorbidity when compared with physical examination. Singletary et al [36] found that most tumors that were detected on breast self-examination by women who were older than 69 years of age were T2 to T4 at presentation in comparison with occult tumors that were detected by mammography in younger women. The American Geriatrics Society Clinical Practice Committee recommends annual or biennial mammography until age 75 and then biennially or every 3 years thereafter in women who have a life expectancy of 4 or more years (Table 2) [37]. The decrease in mammography rates in the elderly is attributable to poor level of function, limitations in activities of daily living, low income, fewer primary care visits, and failure of physicians to recommend or discuss mammography. Attention to reversing these factors improves screening rates [38–41]. The physician’s recommendation, however, is probably the most important stimulus for obtaining screening mammography in older women [42]. In our practice, we tend to recommend mammography for as long as the woman can come in easily for the study. Although this may not increase survival, we believe that it allows us to find smaller cancers that are treated more easily. Treatment As with all malignancies, recommendations for primary treatment of breast cancer should be based on stage at presentation. In a cohort of older women in the United Kingdom, Golledge et al [43] found that women who were older than 70 presented more frequently with T3 and T4 tumors, although the rate of axillary lymph node involvement was similar to that of younger women. Alternatively, Greenfield and coauthors [44], in a 1987 retrospective chart review from UCLA, noted that women who were older than 70 had more stage 1 and stage 2 tumors at diagnosis when compared with women who were 50 to 69 years of age (87% and 81%, retrospectively). Table 2 Breast cancer screening recommendations for older women (ref. 22) Screening modality

Recommendation

Mammography

Annual or biennial mammography until age 75 and biennial or every 3 years thereafter, with no upper age limit for women with an estimated life expectancy of 4 or more years. Annual Monthly

Clinical breast examination Breast self-examination

Data from American Geriatrics Society Clinical Practice Committee. AGS Position Statement: breast cancer screening in older women. J Am Geriatr Soc 2000;48:842–4.

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The National Adjuvant Breast and Bowel Project (NASBP) Protocol B-06 showed that invasive breast cancer could be treated by modified radical mastectomy or by lumpectomy, axillary dissection, and breast radiation [45]. At 26 years of follow-up there was no difference in survival between the two groups [46]. In many cases, elective sentinel lymph node biopsy can be an alternative to axillary dissection [47]. When given a choice, women who are aged 70 and older are more likely to choose breast-conserving surgery than mastectomy [31]. Older women should be offered the option of breast preservation, because body image and the loss of a breast is an important issue, regardless of age. Older patients consistently receive standard breast cancer treatments less frequently than younger patients, even when controlling for comorbidity, cognitive status, and functional status. Yancik et al [4] found that surgery was performed less frequently in women who were older than 85 years than in younger women. Bergman et al [48] found that older women had less extensive surgical procedures and less adjuvant radiation. The decreased use of radiation or surgery may be interpreted as substandard care or as appropriate care, depending on the characteristics of the patient and of the tumor. Most elderly patients can undergo surgery with minimal morbidity. Operative mortality rates for mastectomy that is performed under general anesthesia are approximately 1% [49,50]. Although surgery and anesthesia are not risk-free, the main factor that influences surgical morbidity is comorbidity [48]. The complication rate in women who are older than 65 is reported to be low and usually is related to local wound problems [51]. Short-term decrease in cognitive function after general anesthesia in the elderly also was documented [52]. Older women tolerate breast irradiation as well as younger women [53]; however, elderly patients may find that 6 weeks of radiation therapy is exhausting and may have difficulty arranging transportation. The Milan 3 Trial found that in women who were treated with quadrantectomy without breast irradiation, those who were younger than 45 years of age had an ipsilateral breast tumor recurrence rate of 17.5%, compared with a rate of 3.8% in women who were older than 55 [54]. More importantly, it is not proven that local recurrence influences survival greatly. Standard treatment for breast cancer has similar disease-free and overall survival rates in older and younger women; however, older women have more deaths from nonbreast cancer illness (11% versus 2%; P = .0006) [55,56].

Management of the axilla Axillary dissection is used to stage the disease, to help make treatment decisions, to gain prognostic information, and to prevent axillary

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recurrence. For patients who have small estrogen or progesterone (ER/PR) receptor–positive tumors in whom chemotherapy is unlikely to be used, it may be reasonable to exclude axillary evaluation and to treat the patient with lumpectomy, radiation, and tamoxifen. One retrospective study of elderly patients, aged 70 to 92 years, who were treated with lumpectomy plus tamoxifen but without radiation or axillary dissection, showed that at 5 and 10 years after initial surgery, relapse rates in the ipsilateral axilla were 4.3% and 5.9%, respectively [57]. Cancer and Leukemia Group B (CALGB) performed a randomized clinical trial for women 70 and over who had T1-clinical N0M0 ER/PR–positive breast cancer [58]. All participants were treated with lumpectomy plus tamoxifen and were randomized to receive breast radiation or no further treatment. At a median of 5 years of followup, none of the 200 women who received radiation therapy plus tamoxifen, but no axillary dissection, had axillary recurrences. Of the 204 who had lumpectomy plus tamoxifen but no axillary dissection, two patients (1%) had an axillary recurrence. Accordingly, axillary recurrence is rare in older women who have favorable ER-positive tumors with or without radiation. Axillary lymph node dissection can be associated with significant posttreatment morbidity, including lymphedema, pain, and decreased upper extremity range of motion [59,60]. Complications that involve decreased use of an upper extremity can be especially debilitating in the elderly who often are teetering on the edge of being unable to care for themselves. There are, of course, some patients in whom axillary treatment or evaluation is necessary. In women who have large tumors, ER/PR-negative markers, or clinically-positive axillary nodes, axillary dissection represents the most effective method to decrease local recurrence and to obtain useful treatment information. Sentinel lymph node mapping, which identifies the first node that drains the breast, may prove to be an accurate and preferable alternative to axillary dissection in older patients.

Radiation therapy Should radiation therapy be used after breast-conserving surgery in the elderly? Radiation therapy has been shown repeatedly to reduce the rate of local recurrence in all age groups. Recently, the Early Breast Cancer Trialists’ Collaborative Group (EBCTG) showed in a meta-analysis that ipsilateral breast tumor recurred in 27.2% of patients who did not receive radiation therapy after breast conservation [61]. Those who underwent breast irradiation had a local recurrence of 8.8% (P \ .00001). The EBCTG overview analysis did not show a survival advantage for radiation therapy. At 20 years of follow-up, the decrease in cancer-related deaths in patients who underwent radiation was offset by mortality from other causes [61]. Although the elderly are able to tolerate radiation treatments as well as their younger counterparts [62,63], some investigators suggest that the schedule

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and duration of adjuvant breast radiation may be an obstacle for older patients. Sandison et al [29] found that only one of 31 patients who was offered radiation refused secondary to scheduling problems. Short- and long-term morbidity, including chest wall pain, rib fracture, pneumonitis, and fibrosis are associated with radiation therapy [59,60]. These can be especially problematic in patients who are elderly or ill. Some patients are too debilitated to undergo radiation treatments. In such patients, the addition of radiation therapy has little survival benefit over surgery alone. Shorter life expectancy, especially in women who have comorbid conditions, translates into a decreased length of time in which an elderly patient is at risk for recurrence. In patients who have ipsilateral recurrence and who did not receive radiation, re-excision and radiation are an option. Liljegren et al [64] reported that 11 of 37 (30%) patients who had ipsilateral breast cancer recurrence were able to undergo repeat wide excision plus radiation. Conservative salvage treatment also was reported in 18 out of 28 (64%) patients by Veronesi [54] and in 43% of patients (46 of 108) by Clark et al [65]. Tamoxifen has been suggested as a substitute for radiation to decrease local recurrence in subsets of women who have favorable tumors. NASBP B-21, a prospective trial, randomized 1009 women who had ER-positive cancers that were up to 1 cm in diameter to tamoxifen alone, tamoxifen plus radiation, and radiation plus placebo. Cumulative incidence of ipsilateral breast tumor recurrence was 16.5% with tamoxifen alone, 9.3% with radiation, and 2.8% with tamoxifen plus radiation [66]. When women who were 70 years of age or older were examined, the ipsilateral breast cancer recurrence rate was 1.3% per year in those who were randomized to tamoxifen alone, regardless of ER status [67]. Preliminary data from Hughes et al [58] also showed that women who were 70 years of age and older who were treated with wide excision and tamoxifen alone had a 1.3% recurrence rate at 28 months. Tamoxifen and aromatase inhibitors to prevent distant metastasis Aside from its effect on Ipsilateral Breast Tumor Recurrence (IBTR), tamoxifen is useful for decreasing distant metastasis and increasing survival. A study from the Eastern Cooperative Oncology Group randomized women who were aged 65 to 84 years and had node-positive breast cancer to 2 years of tamoxifen or placebo [68]. The median time to recurrence was 4.4 years with placebo and 7.4 years with tamoxifen. At 2 years, the survival between the two groups was the same. NASBP Protocol B-14 showed a significant increase in disease-free survival in postmenopausal women who were node-negative and receptorpositive that were subsequently treated with tamoxifen [69]. The EBCTG overview of tamoxifen trials also concluded that patients who are estrogenreceptor positive receive a significant benefit from the addition of tamoxifen

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[70]. With the use of adjuvant tamoxifen for 5 years, the proportional reduction in recurrence during approximately 10 years of follow-up was 47%, whereas the proportional reduction in mortality was 26%. The absolute improvement in 10-year survival was 10.9% for patients who were node positive (61.4% versus 50.5%, P \ .00001) and 5.6% for patients who were node negative (78.9% versus 73.3%, P \ .0001) patients. There was a 47% decrease in the rate of contralateral breast cancer. Based on these and other studies, the use of tamoxifen in older women has become standard therapy, although no trials have measured efficacy directly in this age group. Overall, in women who are 70 years of age or older and have ER-positive tumors, tamoxifen seems to have substantial benefit with minimal risk. This is especially true in patients who undergo breast conservation; tamoxifen decreases the risks of ipsilateral and contralateral breast cancer and the risk of distant recurrence. Postmenopausal women can now consider the use of aromatase inhibitors (AIs) as an alternative or follow-up treatment to tamoxifen. These drugs include anastrozole, letrozole, and exemestane. AIs function by suppressing endogenous estrogens to extremely low levels. The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial, a randomized trial in postmenopausal women who had operable breast cancer, showed in its first analysis that the use of anastrozole resulted in a longer, distant disease–free survival and time-to-recurrence than tamoxifen [71]. In the recent ATAC trial efficacy and safety update, anastrozole continued to show improved disease-free survival (86.9% to 84.5%, P = .03) and increased time-torecurrence (P = .015), especially in hormone receptor–positive cancers [72]. Furthermore, the study by Goss and colleagues [73] showed that women who had completed 5 years of tamoxifen, when randomized to letrozole versus placebo, had estimated 4-year disease-free survival rates of 93% and 87%, respectively (P \ .001). These data suggest that AIs may be more effective than tamoxifen and, with confirmatory studies, may become the adjuvant endocrine therapy of choice [74].

Endocrine therapy alone as treatment Originally, the use of tamoxifen alone for initial treatment of localized breast cancer was studied in women who were not candidates for surgery. In a study by Preece et al [75], 67 women who were aged 75 years and older who had clinically-localized breast cancer were treated with tamoxifen alone, without surgery. Seventy-three percent responded to treatment. Fiveyear survival was 49.4% and was greatest for those who showed an initial complete response. Other studies found that up to 63% of patients who were treated with tamoxifen alone as a first-line treatment had tumor regression [76]. The median time of response to tamoxifen was 13.5 weeks and tumor regression

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persisted for up to 5 years in one third of patients; however, high relapse rates, that often required additional local treatment were found during follow-up [77]. AIs also may have a role in definitive therapy in older, frail patients. In a recent nonrandomized trial, the preoperative use of exemestane, an AI, showed greater reduction in tumors that were larger than 3 cm than was noted previously with tamoxifen [78]; however, in another small, randomized study of tamoxifen versus letrozole, there was no difference in tumor regression [79]. Endocrine therapy as primary treatment is of value only in women who have receptor-positive breast cancer whose coexisting illnesses render them unable to tolerate surgery or in those who refuse surgical treatment. Recently, AIs have been proposed as preoperative therapy in older patients. Eiermann and his colleagues performed a randomized, prospective trial comparing letrozole and tamoxifen in postmenopausal women with ER and/or PR-positive breast cancers who were not candidates for breast conservation [80]. The overall response rate assessed by clinical examination was higher in the letrozole group (55%) when compared to tamoxifen (36%) (P \ .001). Furthermore, in a small study by Miller and Dixon [78], 8 out of 10 patients who would have required mastectomy before treatment with an AI were able to undergo breast-conserving surgery. AIs play a role in making breast-conserving surgery feasible. Chemotherapy The use of adjuvant chemotherapy in the elderly has not been studied directly. Chemotherapy is underused in older women, despite the fact that treatment of locally advanced and metastatic disease indicates that the elderly can tolerate treatment [9,81,82]. Age is an independent predictor of physician recommendation for cytotoxic therapies; however, older age does not seem to influence patient acceptance of treatment recommendations [83,84]. The meta-analysis by the EBCTG looked at the effect of age on results of adjuvant chemotherapy [85]. Use of chemotherapy resulted in a 10% reduction in death from breast cancer in women who were 60 to 69 years of age. Because there was a small numbers of participants who were older than 70, there was no discussion of the results in this age group. Women who up to 40 years of age had a 37% reduction in recurrence and a 28% reduction in deaths from breast cancer, whereas women who were between 20 and 69 years of age had an 18% reduction in recurrence and a 9% reduction in deaths from breast cancer. Recently, the International Breast Cancer Study Group compared cyclophosphamide, methotrexate, and 5-Fluorouracil (5-FU) (CMF) with tamoxifen [86]. They found a 15% survival advantage with chemotherapy in patients who were between 60 and 80 years of age and had ER-negative tumors. In contrast, the group that had ER-positive tumors obtained no benefit from combination treatment.

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Chemotherapy regimens may need to be tailored to the older patient. When standard-dosage CMF chemotherapy is used in patients who are between 65 and 90 years of age for the treatment of advanced breast cancer, toxicity is increased. If dosages are decreased to complement creatinine clearances, toxicity levels are similar to those in younger patients but response rates may diminish [87]. Older patients must be assessed for adriamycin tolerance and should have an adequate life expectancy to receive treatment-based mortality advantages. Chemotherapy may be most beneficial for patients who have ER-negative tumors and few comorbid conditions.

Summary of management Screening Annual clinical breast examination and monthly breast self-examination are recommended for all women. Annual mammography is recommended up to 75 years and should be continued after age 75 in women who have few limiting comorbid conditions and reasonable life expectancy. Compliance with mammography is best if recommended by the primary care physician. Local definitive therapy There is no universal approach for managing the primary tumor in older women who have breast cancer. Recommendations must be individualized to the patient and the tumor presentation. Table 3 gives a synopsis for the treatment of a primary breast cancer. Healthy women who present with large, ER-positive tumors that cannot be treated with breast conservation can be given preoperative hormonal therapy in an attempt to convert to breast-conserving surgery or can undergo a simple mastectomy with sentinel node biopsy. Healthy patients who have large, ER-positive tumors and clinically-positive axillary nodes also can be given preoperative hormonal therapy to try to convert to conservation or can have a modified radical mastectomy. Healthy women who present with large, ER-negative tumors that cannot be treated with breast conservation should undergo a simple mastectomy with sentinel node biopsy. Candidates for breast conservation include patients who have small tumors relative to breast size. Those who are surgical candidates and have clinically-positive nodes are treated best by lumpectomy and axillary node dissection followed by breast radiation. Those who have clinically-negative nodes and ER/PR-negative tumors or who have a high probability of positive nodes and who are potential candidates for adjuvant postoperative chemotherapy should be considered for lumpectomy and sentinel lymph node biopsy followed by radiation.

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Table 3 Treatment recommendations for management of a primary breast cancer Conservation possible

ER/PR status

Clinical node status

Health statusa

Suggested treatment

No

Positive

Negative

Poor

No

Positive

Positive

Poor

No

Positive

Negative

Good

No

Positive

Positive

Good

No

Negative

Negative

Good

No Yes

Negative Positive

Positive Negative

Good Good

Yes

Negative

Negative

Good

Yes

Positive

Positive

Poor

Yes

Positive

Positive

Good

Tamoxifen or an aromatase inhibitor Tamoxifen or an aromatase inhibitor Preoperative hormonal therapy to try to convert to conservation or simple mastectomy with sentinel node biopsy Preoperative hormonal therapy to try to convert to conservation or modified radical mastectomy Simple mastectomy with sentinel node biopsy Modified radical mastectomy Lumpectomy with or without sentinel node biopsy Lumpectomy with sentinel node biopsy Tamoxifen or an aromatase inhibitor Lumpectomy and axillary dissection

a

Poor health means limited life expectancy.

Primary hormonal therapy (tamoxifen or an AI) can be used in patients who have large or small ER- or PR-positive tumors who are too frail to have surgery or have limited life expectancy. Some patients are not surgical candidates and have ER-negative tumors. Individualized treatment and open discussions with the patient and family are essential. Systemic adjuvant therapy Adjuvant hormonal therapy should be considered in all postmenopausal women who have hormone receptor–positive tumors. Tamoxifen has been the standard hormonal therapy for postmenopausal women. There is increasing use of AIs as second-line therapy after relapse on tamoxifen or as primary therapy in women who have contraindications to tamoxifen (eg, history of endometrial malignancy or thromboembolic events). Only older women who have an extremely low risk of distant metastases or severe comorbid illness should not be offered endocrine therapy. Adjuvant chemotherapy should be considered for older women whose risk of systemic recurrence is high and who are in good health and have an estimated

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survival of at least 5 years. Chemotherapy is most beneficial in older women who have ER-negative tumors that exceed 2 cm and have negative lymph nodes or tumors of any size that have significant nodal involvement. For older women who have ER-positive or PR-positive tumors, there only is a small benefit of chemotherapy over tamoxifen alone, even in those who have positive lymph nodes. The authors recommend radiation therapy after breast-conserving surgery to patients who have tumors that are larger than 2 cm, regardless of ER status. In patients who are taking tamoxifen and have small (\2 cm) tumors that are ER-positive and clinically node-negative, radiation may not be needed. It is hoped that the results of CALGB 9343 will shed some light on this issue.

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