Breast Cancer Treatment in Older Women

8/14/2019 Breast Cancer Treatment in Older Women

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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

aDivision of Surgical Oncology, Massachusetts General Hospital,

100 Blossom Street, Cox 626, Boston, MA 02114, USAbGreater 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 substantial16 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 2004 Elsevier Inc. All rights reserved.

doi:10.1016/j.soc.2004.07.006

Surg Oncol Clin N Am

14 (2005) 85102
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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 thepresence of comorbid conditions (eg, heart disease, diabetes, other cancers,

respiratory illnesses) and was related inversely to patient age. There was a 20-

fold 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 diseasepresentation, 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

Table 1

Average remaining lifetime at various ages according to race, preliminary data from 2001

Life expectancyAge (y) White women (y) Black women (y)

60 23.5 21.5

65 19.5 17.9

70 15.7 14.7

75 12.3 11.8

80 9.3 9.2

85 6.7 7.0

90 4.8 5.3

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

86 M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85102


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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 over-

treatment. Of those who received breast-conserving surgery, many did notundergo axillary dissection and were not followed by radiation therapy

possible under treatment [810].

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 teachinghospitals 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 thedearth 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 receptorpositive 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 metastasesincreasing 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

87M. Howard-McNatt et al / Surg Oncol Clin N Am 14 (2005) 85102


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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 olderwomen. 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 youngwoman. 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 thatwas 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 differ-

ences 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. Theyseek advice from physicians, but they also tend to use such tools as the

Internetbe it good or badto 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 activitiesof daily living, religious commitments, transportation, and attitudes

concerning death. Such concerns strongly influence the patients 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 meta-analysis 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 cancerrelated 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 aged65 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 useful-

ness 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 mammo-

gram 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 mosttumors 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, fewerprimary care visits, and failure of physicians to recommend or discuss

mammography. Attention to reversing these factors improves screening

rates [3841]. The physicians 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 1987retrospective 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.

Clinical breast examination Annual

Breast self-examination Monthly

Data from American Geriatrics Society Clinical Practice Committee. AGS Position

Statement: breast cancer screening in older women. J Am Geriatr Soc 2000;48:8424.



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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 generalanesthesia 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 3Trial 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)

receptorpositive tumors in whom chemotherapy is unlikely to be used, it

may be reasonable to exclude axillary evaluation and to treat the patientwith 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/PRpositive 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 follow-up, 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 oftenare 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 underwentbreast 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 arean 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 plusradiation, 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 betweenthe 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 receptor-

positive that were subsequently treated with tamoxifen [69]. The EBCTG

overview of tamoxifen trials also concluded that patients who are estrogen-

receptor 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%. Theabsolute 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; tamoxifendecreases 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 diseasefreesurvival 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-to-

recurrence (P = .015), especially in hormone receptorpositive 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 theadjuvant 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 tamoxifenalone, without surgery. Seventy-three percent responded to treatment. Five-

year 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, random-

ized 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 inmaking 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 doesnot 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 anda 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 canundergo 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 haveclinically-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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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 surgicalcandidates 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 receptorpositive 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 asprimary 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

Table 3

Treatment recommendations for management of a primary breast cancer

Conservationpossible

ER/PRstatus

Clinicalnode status

Healthstatusa

Suggestedtreatment

No Positive Negative Poor Tamoxifen or an aromatase

inhibitor

No Positive Positive Poor Tamoxifen or an aromatase

inhibitor

No Positive Negative Good Preoperative

hormonal therapy to try

to convert to conservation

or simple mastectomy with

sentinel node biopsy

No Positive Positive Good Preoperative hormonal

therapy to try to convert

to conservation or modified

radical mastectomy

No Negative Negative Good Simple mastectomy with


No Negative Positive Good Modified radical mastectomy

Yes Positive Negative Good Lumpectomy with or without


Yes Negative Negative Good Lumpectomy with sentinel

node biopsy

Yes Positive Positive Poor Tamoxifen or an aromatase

inhibitor

Yes Positive Positive Good Lumpectomy and axillary

dissection

a Poor health means limited life expectancy.



14/18

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. Forolder 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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