Management of Breast Cancer in Older Women
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Tamoxifen was, however, more commonly used on the older women compared to the younger, and the difference seems to increase with increasing stage Table 3. A lower proportion of those 70 y and older are treated in the referral hospital, stage by stage. For the stages III—IV and the unstaged Table 4 , there was an increased proportion of unknown proliferation status and estrogen receptor status in the older age groups. There were also a decreasing number of examined lymph nodes by age in those undergoing axillary dissection. Regarding the treatment characteristics for stages III—IV and the unstaged, the pattern is essentially the same as for stages I—IIB, with a lower treatment activity amongst the oldest.
Although the low treatment activity index for stage III and for the unstaged is quite high for both age groups, it is higher for the older women. The older women in stages III—IV also more often did not receive any surgery at all, and, as in earlier stages, radiotherapy was much less used in the elderly as was chemotherapy. The difference in the use of tamoxifen was only present in the unstaged.
A difference, as compared to the earlier stages of breast cancer, is that the differences by age group in the proportion of women treated at the main hospital of the county were not as pronounced in the higher stages. Due to the nature of the disease in the higher stages, omitting surgery is much more common in stages III and IV than in earlier stages.
However, the choice not to resect the tumor is much more common in the elderly than in the age group 50—69 y. Table 5 shows the result of the statistical models in which the RER is elevated for the elderly in all models in stages IIB and higher, since these were the stages in which we found differences by age group in relative survival see last lines of Table 3 and 4.
The simpler model, which only adjusts for year of diagnosis, shows the highest RER for the older, whereas the other models tend to lower the RER as diagnostic activity, refined stage definition by including number of involved lymph nodes and tumor size , and, finally, treatment are taken into account.
In the final model, the RER for the older age group is no longer statistically significantly elevated, and any tangible difference only remains for women in stage IIB, with an RER of 1. We found three statistically significant interactions of 12 examined between age and type of treatment and excess mortality, all within stage III.
The RER, comparing women not receiving any surgery to those receiving surgery, was four times higher among the younger compared to the older RER 6. We found large and clinically relevant absolute survival differences disfavoring women aged 70—84 y as compared to women aged 50—69 y. Due to the Swedish mammography screening policies, the stage distribution was more unfavorable among the older, but an adjustment for stage could only partly explain the survival differences.
Looking at relative survival stage by stage, the prognosis was worse in stage IIB and higher among women over 70 y as compared to those 50—69 y. Adjusting for these factors in models largely explained the differences by age group, except for women in stage IIB. Our large population-based register lends further strong support to previous reports [ 4 , 9 , 10 ] that there is an age bias in management of older women.
We used a population-based database with high coverage and little misclassification of the variables used in this analysis. Another strength is that relative survival provides a measure of the excess mortality experienced by breast cancer patients, irrespective of whether excess mortality is directly or indirectly attributable to cancer [ 8 ].
Therefore, we could study the excess mortality adjusting for the expected survival in the background population and thereby largely compensate our comparisons for mortality due to co-morbidity. However, a drawback of the study is the lack of information on co-morbidity. Co-morbidity may have provided rational reasons for withholding diagnostic measures or specific treatments.
One recent study has, however, found non-rational differences in treatment among older women even after controlling for co-morbidity [ 11 ]. It would also have been interesting to know whether socioeconomic status is a determinant for survival, but in essence this would not have justified an eventual age bias in management.
An important explanation for the poorer survival among the elderly was the unfavorable stage distribution due to considerably less mammography screening activity after 70 y and no screening taking place after 74 y. This explanation points to an important health policy issue as the population ages. In many Western countries today, a y-old woman has a life expectancy of 12—16 y. In stages IIB and higher, radiotherapy was less often used in older women, and this could not be explained only by the less frequent use of breast conservation in the elderly. Radiotherapy in itself, although very effective in reducing relapses also among elderly [ 2 , 12 ] and generally well tolerated in higher age groups [ 13 ], will not have a major impact on mortality.
However, the use of radiotherapy upon adequate indications may, in register data, be a proxy variable of the use of multidisciplinary management and compliance to clinical recommendations. Only a very small proportion of the older women received chemotherapy.
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This is a consequence of the fact that the guidelines during this time period often have suggested upper age limits of 65—70 y for recommending chemotherapy. The evidence base for effectiveness of chemotherapy in the elderly is considered weaker than for younger women and only a few studies of the effect of chemotherapy have included women over 70 y [ 2 ].
We only found an effect of modification of treatment in stage III, and not in stage IIB and unstaged, strengthening these findings. Moreover, co-morbidity has been found not to be an adequate explanation for why clinicians decide to use chemotherapy [ 4 ], and age alone seems to be an important indicator of the likelihood to receive adjuvant chemotherapy [ 5 ]. The survival differences by age group found in our study and studies by others point also to the importance of further investigating effective adjuvant systemic treatments in the elderly.
Tamoxifen was widely used in older women in our study. One possible reason for the difference in use to the disadvantage of the younger patients is that during the first half of the s, tamoxifen was considered to have a negligible effect in younger patients and was therefore not given to those who received chemotherapy. However, we also found that with higher age, an increasing proportion of women with receptor-negative tumors were treated inappropriately with tamoxifen. A possible interpretation of this finding is that clinicians felt that some treatment activity is warranted in women perceived to have a moderate or high risk of recurrence, but that, in the absence of guidelines regarding chemotherapy, the clinician took the chance that tamoxifen would provide some benefit but little harm.
In summary, elderly women were disfavored in several ways: less use of mammography screening, lower diagnostic activity, and lower treatment activity, leading to a lower relative survival. There is an acute need for more empirical evidence about the effectiveness and tolerability of different treatments in elderly women. Likewise, it is probable that better structured guidelines for elderly women would be a means to improve the situation. The study was supported by grants from the Swedish Cancer Society.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. SE performed all of the analyses, contributed to the interpretation of the data, and drafted the article. PWD contributed with the analysis and interpretation of the data.
LB contributed with the acquisition of the data, with detailed knowledge about the register, and with revising the article for intellectual content. LH contributed with the conception and the design of the study, interpretation of the data, and revising the article for intellectual content.
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Breast cancer is the most common cancer in women in much of the developed world; for example, there are 41, new cases in the UK per year. In , 6, women were diagnosed with breast cancer in Sweden. Survival has improved greatly; in the past ten years in the UK, the risk of dying of the disease has fallen by one-fifth. The disease is rare in women under 30 years, but the risk of breast cancer increases with age. Although there are a number of treatments for breast cancer, previous work has suggested that certain factors may affect whether a woman gets treatment.
The U. Preventive Services Task force recommends screening every other year for women ages 50 to It offers no guidance for women 75 and older because there isn't enough evidence to indicate whether the benefits outweigh the risks for women in that age group. Instead, the best advice is to decide whether to continue having regular mammograms based on your health and other preferences. If your life expectancy isn't at least 10 years, it doesn't make sense to get mammograms. But if you're in great health and may have 25 or 30 years ahead of you, you may want to get mammograms," Dr.
Burstein says. For older women, treatment for most early breast cancer is likely to be relatively gentle. Such tumors are treatable with aromatase inhibitors—which cut the body's production of estrogen and include anastrozole Arimidex , exemestane Aromasin , and letrozole Femara —or tamoxifen Genox, Istubal, Nolvadex, and Valodex , which keeps estrogen out of cancer cells.
The treatment of early breast cancer in women over the age of 70
A major study demonstrated that women over 70 with this type of tumor who were treated with lumpectomy and hormone therapy alone lived just as long as those who underwent radiation as well, although radiation reduced the risk of a recurrence somewhat. Women who have other health conditions may choose to forgo radiation, while those who are healthy may choose to have breast radiation to reduce the risk of a recurrence when they are older and more vulnerable.
Patients with low p16 expression may have not aged as quickly and may have a good degree of reserve, either in white cells, immune cells, or liver or kidney cells. These patients might do well with treatment. Patients with high p16 expression are more likely to have white cells that do not proliferate as well, that is, are the most senescent, and thus greater myelosuppression. Researchers have been measuring p16 RNA levels in the T cells of peripheral blood samples as a marker of aging. This method, in addition to standard geriatric assessment and comorbid illness evaluation, may provide clinicians with a molecular tool for estimating survival as well as treatment toxicity.
Expression of p16 INK4a in peripheral blood T-cells is a biomarker of human aging.
Women Older Than 65 Have Worse Outcomes After Breast Cancer Diagnosis
Aging Cell ;—, with permission. In the adjuvant treatment of breast cancer in both older and younger patients, the goal is to improve the curability of the patient. Clinicians need to realize that, in older patients, the recurrence risk is similar to that of younger patients when adjusting for stage, and that life expectancy is the key to decision making.
Life expectancy is based on comorbidity and physical function, and healthy elders should therefore be considered for the same treatments as younger patients. Undertreatment has been linked to poor outcomes, regardless of patient age.
The treatment of early breast cancer in women over the age of 70 | British Journal of Cancer
One analysis focused on distant disease-free survival in patients treated according to the St. Gallen treatment guidelines, such as receiving postoperative breast radiation or taking tamoxifen, versus patients whose treatment did not conform to these simple guidelines. Clinicians should therefore be careful not to undertreat older patients based on age alone Fig. Compliance with consensus recommendations for systemic therapy is associated with improved survival of women with node-negative breast cancer. J Clin Oncol ;— Reprinted with permission. In breast cancer management, it is helpful to think of three distinct subtypes of breast cancer.
This is also the most common presentation in older breast cancer patients. These patients are a very heterogeneous group and are divided into luminal A patients, who have high ER expression and do well with endocrine therapy, and luminal B patients, who realize more benefit with chemotherapy and less benefit from endocrine therapy. Other subtypes include the HERnegative ER-negative progesterone receptor—negative, or triple-negative, population. The major question in many older patients concerns the added value of chemotherapy in the large population of ER-positive HERnegative patients.
Tamoxifen, in particular, has been demonstrated to have value in older patients. Tamoxifen for 5 years: Decreasing annual odds for recurrence or death year follow-up. Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and year survival: An overview of the randomised trials. Lancet ;—, with permission. Aromatase inhibitors are now available, and their role is being better defined as trials mature. However, it is important to consider these agents in the elderly, if possible, because of their low toxicity profiles.
Unlike tamoxifen, there are no greater risks for vascular events, endometrial cancer, or other toxicities associated with aromatase inhibitors. Reflective of the American Society of Clinical Oncology guidelines, aromatase inhibitors should be considered for all postmenopausal women at some time in their course of treatment, and perhaps as an initial treatment for many older patients [ 9 ]. One large international cooperative group study conducted by the National Cancer Institute of Canada compared letrozole with placebo in women who had received 5 years of tamoxifen as adjuvant therapy.
These findings were somewhat reassuring about the toxicity profile of letrozole and its use in older patients Fig. Efficacy, toxicity, and quality of life in older women with early-stage breast cancer treated with letrozole or placebo after 5 years of tamoxifen: NCIC CTG intergroup trial MA. Online is another helpful tool for evaluating therapeutic effect in older patients. This program is unique because it takes into account U. In addition, users can input an estimate of comorbidity or coexisting illness [ 11 ]. To demonstrate the utility of Adjuvant!
Online, a case was plotted of a patient 71 years of age, presenting with a 2-cm, grade 2, node-positive, hormone receptor—positive breast cancer. The program estimates year survival data and illustrates the relative value of chemotherapy Fig. Entering data into Adjuvant! There is a modest improvement with chemotherapy regimens such as cyclophosphamide, methotrexate, and fluorouracil CMF or doxorubicin and cyclophosphamide AC for four cycles, and perhaps even more improvement when using more aggressive chemotherapy in this group.
Meanwhile, the same analysis in patients with poor health suggests that only one third survive at 10 years because of their comorbid illnesses. In addition, the benefits of all therapies are diminished. In this way, Adjuvant! Online can help clinicians use comorbidity, in addition to age, to make treatment decisions [ 11 ]. Ten-year survival: value of chemotherapy. Patient aged 71 years with 2. Based on information from Adjuvant! Another recent analysis from the Arimidex, Tamoxifen, Alone or in Combination trial used the Onco type DX genome assay in patients who had received tamoxifen or an aromatase inhibitor and had not received chemotherapy [ 12 ].
In that analysis, even patients with one to three positive nodes who had very low recurrence scores tended to do well with endocrine therapy alone and had very low probabilities of distant metastasis at 10 years. In patients with four or more nodes, there was a higher risk for recurrence, even with low recurrence scores. Onco type DX, which as a genetic tool is more accurate in factoring in the degree of ER expression and tumor grade, has the potential to be a valuable tool in clinical decision making for older patients [ 12 ].
With the addition of taxanes and other more aggressive therapies, including new treatments, these results will continue to improve. These findings confirm that older, healthy patients with triple-negative breast cancer should be considered for treatment with state-of-the-art chemotherapy. Abbreviations: AC, doxorubicin and cyclophosphamide; CMF, cyclophosphamide, methotrexate, and fluorouracil. Adjuvant chemotherapy in oestrogen-receptor-poor breast cancer: patient-level meta-analysis of randomised trials.
Lancet ;—40, with permission from Elsevier. Researchers were hoping that capecitabine would be noninferior in older patients, providing clinicians with an adjuvant approach to older patients with breast cancer who faced issues related to more aggressive i. They found that standard therapy was better than capecitabine, with marked, highly significant longer relapse-free and overall survival times favoring standard chemotherapy with CMF or AC. In an unplanned subset analysis, the researchers confirmed that the greatest therapeutic benefit in these older patients was in those with triple-negative breast cancer.
Overall, there was a marked improvement in patients with triple-negative breast cancer that favored standard chemotherapy, which underscores the value of chemotherapy in older patients with the triple-negative phenotype. There were no differences in outcome among the regimens for patients with hormone receptor—positive tumors Fig. Relapse-free and overall survival by treatment regimen and hormone receptor status. The Kaplan—Meier plot of this unplanned analysis for both relapse-free and overall survival is shown above.
The dashed lines indicate patients treated with CMF or AC, and the solid lines indicate patients treated with capecitabine. The panels on the left show relapse-free survival.