Breast Radiotherapy: Considerations in Older Patients

With an ageing population, the number of older women with breast cancer eligible for adjuvant irradiation after breast conserving surgery and mastectomy is rising. There is a dearth of level 1 data on the effect of adjuvant irradiation on local control, quality of life and survival. In large part this reflects the exclusion of patients over the age of 70 years from randomised trials. The prevention of local recurrence may reduce the risks of dissemination. However, older women with early breast cancer and a life expectancy of less than 5 years are unlikely to derive a survival benefit from adjuvant radiotherapy. Rates of access of older patients to adjuvant irradiation are lower than for younger patients. Physician and patient bias and co-morbidities are contributory factors. There are also competing risks of mortality from co-morbidities, particularly in women over the age of 80 years. Postoperative radiotherapy after breast conserving surgery does not seem to compromise overall quality of life of older patients. Although the absolute reduction in local recurrence from adjuvant radiotherapy is modest in lower risk older patients after breast conserving surgery and adjuvant systemic therapy, there has to date been no group of fitter old patients defined from whom radiotherapy can be reasonably omitted. Guidelines for postmastectomy radiotherapy should not differ from younger patients. Adequately powered randomised trials are needed to assess the effect of adjuvant irradiation in older patients on outcomes after breast conserving surgery and mastectomy to provide a more robust basis for evidence-based radiotherapy practice.     

Qualitative age interactions in breast cancer studies: a mini-review

A qualitative age interaction is defined as the reversal of relative risks or rates according to age at onset, and is often evident in studies that examine the etiology, prognosis and treatment of breast cancer. For example, incidence rates (or risks) are higher for aggressive when compared with indolent breast cancers prior to age 40-50 years, after which rates are higher for indolent tumors. Nulliparity and obesity decrease breast cancer risk in younger women, but increase risk in older women. Curves depicting the annual hazard of breast cancer death are shaped differently for the early- and late-onset tumors. Clinical trials for mammography screening, fenretinide chemoprevention and neo-adjuvant chemotherapy show opposite effects in younger and older women. Finally, high-risk/early onset breast cancers are more common among African-American women than Caucasian women, and this may partly account for the racial survival disparities. Taken together, these examples imply that aging may modify breast cancer risk, prognosis and treatment. These qualitative age interactions (or effect modifications) are important because they suggest that high-risk/early-onset and low-risk/late-onset breast cancers are different diseases, derived from different carcinogenic pathways. When age interactions are suspected, breast cancer studies should be stratified by early versus late age of onset or analyzed age specifically.     

年龄、身体形象和风险信息因素对女性乳腺癌患者手术治疗方式选择的影响

目的 探讨年龄差异、身体形象和风险信息对女性乳腺癌患者手术治疗方式决策的影响.方法 选择两组健康女性样本,一组为18～24岁本科在校学生60人,一组为35～60岁社区健康体检女性60人,受试者拟想自己身患乳腺癌,在获得相关保乳手术和乳房切除术的治疗信息后,选择手术治疗方式,并注明选择理由.结果 年轻与年长女性对身体形象关注度不同,影响对手术治疗方式的选择;面对风险信息,年长女性不太可能选择保乳手术.结论 年龄及对身体形象的关注度影响患者对保乳手术和乳房切除术的选择;风险信息对治疗选择没有直接影响,但风险信息对年轻和年长女性的影响不同.医务人员应为乳腺癌患者提供适龄的有关治疗选择的科学信息,确保治疗方案决策过程中患者的积极参与,同时应关注对治疗手段影响身体形象有不同顾虑程度的患者.     

Breast cancer in adolescents and young women

Breast cancer is very rare in adolescents and very young women. Less than 1% of all breast cancer cases occur before the age of 30 years (Natl Cancer Inst Monogr 16 (1994) 69). Invasive breast cancer occurring in women before the age of 35 years has a more aggressive biological behaviour and is associated with a worse prognosis than in older premenopausal women. Breast cancers in these young women are more frequently poorly differentiated, oestrogen-receptor (ER)-negative, have lymphovascular invasion and high proliferating fractions. Breast-conserving surgery in women <35 years old is associated with a higher risk of local recurrence than in older women. All young women should be considered at moderate-high risk by virtue of their age alone and offered adjuvant therapy. The long-term toxicity of adjuvant therapies is a particular concern when treating these women. The implications of possible fertility impairment and premature menopause require consideration when discussing adjuvant chemotherapy and endocrine therapy. Adolescents and young women are particularly vulnerable to emotional distress and psychosocial problems and should be provided with appropriate support. Young women who are at a potential high-risk of developing breast cancer such as those with germline mutations of BRCA1, BRCA2, TP53, PTEN or who have previously received mantle irradiation for Hodgkin's disease need close follow-up and are candidates for screening from a young age.     

Mutations in the p53 tumor suppressor gene and early onset breast cancer

Among breast cancer patients p53 gene mutation is associated with a poor prognosis. Young women with breast cancer are more likely than older women to have a poor prognosis, but whether p53 gene mutation plays a role in breast cancer in young women is not clear. This study identified 199 breast cancer patients and tested the hypothesis that p53 gene mutation was associated with early onset breast cancer. Patients with p53 gene mutations were 3-times more likely to have an early onset breast cancer (age < or = 40 years at diagnosis) than those without p53 mutations (OR = 3.05, 95% CI = 1.10-8.45). Patients with both missense and silent mutations were 7-times more likely to have a diagnosis of early onset breast cancer (OR = 7.56, 95% CI = 2.22-25.8). Patients with mutations in exon 8 of the p53 gene were 6-times more likely to be diagnosed with early onset breast cancer (OR = 6.48, 95% CI = 1.37-30.6). These findings suggest that p53 gene mutation may hasten the onset of female breast cancer.     

Epidemiology of breast cancer in young women

Breast cancer is mainly a postmenopausal disease, but in younger women breast tumors often exhibit more aggressive features and worse prognosis. Furthermore, high-risk and low-risk tumors present different age distributions suggesting that breast cancer comprises a mixture of two different disease processes. In agreement with this hypothesis, breast cancer presents different epidemiologic traits in pre- and postmenopausal women. Regarding racial distribution, incidence is higher in black women at younger ages in US, while the reverse is true among women older than 50 years. Genetic predisposition is a stronger risk factor in young women. On the contrary, nulliparity and obesity decrease the risk of early-onset breast cancers while are associated with higher incidence in older women. Epidemiologic data related with the hormonal exposure in utero suggest that the effect is stronger in early breast cancers. In most developed countries, breast cancer has shown an upward trend until recent years in postmenopausal women, while incidence rates in younger women have been stable. However, Spain is an exception to this rule: Spanish women younger than 45 years of age have registered a steady increase of breast cancer that may be related with the remarkable lifestyle changes experienced by women born in the second half of the twentieth century.     

Association of time since last birth,age at first birth and parity with breast cancer survival among parous women: A register‐based study from Norway

Reproductive factors that have a well‐documented effect on breast cancer risk may also influence the prognosis of the disease, but previous studies on breast cancer survival have yielded conflicting results. We combined information from two population‐based registries and obtained information on 16,970 parous women with invasive breast cancer. Cox regression analysis was used to assess breast cancer survival in relation to age at diagnosis, age at first birth, time since last birth and parity. We stratified the analyses by age at diagnosis (<50 and ≥50 years) as an approximation for menopausal age. In women diagnosed before 50 years of age, breast cancer survival was reduced with younger age at diagnosis (p for trend <0.001), whereas in women diagnosed at 50 years or later, survival was reduced with older age at diagnosis (p for trend 0.011). For breast cancer diagnosed before 50 years, survival was poorer in women with four or more births compared to women with one or two births (hazard ratio 1.3, 95% confidence interval 1.1–1.6). A short time since last birth was associated with reduced survival (p for trend 0.05), but adjustment for stage and grade attenuated the association. Among women diagnosed at 50 years or later, we found no association with survival for any of the reproductive factors. In summary, reproductive factors were associated with survival from breast cancer diagnosed before but not after age 50 years. Young women had a particularly poor prognosis throughout the study period.     

Management issues for elderly patients with breast cancer

Opinion statement Fifty percent of breast cancers occur after the age of 65 years and 25% occur after the age of 75 years. Encountering a breast cancer in an older woman is frequent. After years of dearth of data specific to the elderly, some evidence is beginning to accumulate concerning breast cancer in the older woman. Recent data from mammography studies confirm its effectives in women with 10 years or more of life expectancy (perhaps even 5 years). Epidemiologic and randomized studies demonstrate that a proper surgery and adjuvant treatment can decrease relapse and improve survival in patients older than 80 years. Radiation therapy studies show a decrease in local relapse even in patients older than 70 years. Adjuvant hormonal therapy has essentially the same effectiveness as in younger women. Chemotherapy has a role in patients older than 70 years. Consensus statements, such as the St. Gallen consensus, have dropped the age limit of 70 years from their recommendations. Comorbidity and life expectancy should be taken into account for proper selection of adjuvant treatment. The treatment of metastatic breast cancer has evolved significantly with the introduction of aromatase inhibitors, new chemotherapeutic agents, and targeted biologic agents. New chemotherapeutic agents are as effective as single agents compared to older and more toxic drug combinations. The cumulative result of the introduction of these new agents, at a population level, is a 7.5-month increase in the median survival time of patients with metastatic breast cancer over the past decade.     

Breast‐conserving therapy in young women with invasive carcinoma of the breast

Higher local recurrence rates have been reported in young women with invasive carcinoma of the breast treated with breast‐conserving therapy (BCT). However, age itself may not be responsible for this increased risk of recurrence. To investigate this further, a computerized literature search of MEDLINE was performed using data from 1996 to May 2003. The research was limited to female patients with localized, invasive adenocarcinoma of the breast but also included patients of young age with ductal carcinoma in situ. Women of young age with breast cancer, treated with BCT are at an increased risk of recurrence ranging from 7.5 to 35%. However, the data would suggest that the increased risk is secondary to the association of young age with more aggressive tumours and a positive family history of breast cancer. Other factors that may explain the adverse prognosis in women of a young age include associated genetic abnormalities and the lack of mammographic screening programmes for women of young age. Young age is a risk factor for breast recurrence after BCT. However, management decisions should be based on tumour stage, grade and other related prognostic features rather than on young age alone.     

The influence of aging on the early detection,diagnosis, and treatment of breast cancer

Patterns of care for women with breast cancer vary substantially with patient age. Older patients with breast cancer frequently receive less than standard management, resulting in poorer outcome. At diagnosis, the health status of older women with breast cancer affects survival and treatment decisions. Age-related comorbidity may limit diagnostic tests, narrow treatment options, and significantly increase mortality not related to breast cancer. Yet, for healthy older women with early-stage breast cancer, stage-adjusted survival is similar to that of younger women. Calendar age is not sufficient to encompass the heterogeneity in health status of the elderly. Instead, management of older women with breast cancer should be based on anticipated survival, functional status, and the goals of the patient for treatment. In this review, we evaluate pertinent data and provide guidance for the management of older women with breast cancer.     

Is there evidence of age bias in breast cancer health care professionals’ treatment of older patients?

ObjectivesDespite NICE (2009; 2018) guidelines to treat breast cancer patients ‘irrespective of age’, older women experience differential treatment and worse outcomes beyond that which can be explained by patient health or patient choice. Research has evidenced the prevalence of ageism and identified the role of implicit bias in reflecting and perhaps perpetuating disparities across society, including in healthcare. Yet age bias has rarely been considered as an explanatory factor in poorer outcomes for older breast cancer patients.MethodsThis mixed methods study explored age bias amongst breast cancer HCPs through four components: 1) An implicit associations test (31 HCPs)2) A treatment recommendations questionnaire (46 HCPs).3) An attitudes about older patients questionnaire (31 HCPs).4) A treatment recommendations interview (20 HCPs).ResultsThis study showed that breast cancer HCPs held negative implicit associations towards older women; HCPs were less likely to recommend surgery for older patients; some HCPs held assumptions that older patients are more afraid, less willing and able to be involved in decision-making, and are less willing and able to cope with being informed of a poor treatment prognosis; and conditions which disproportionately affect older patients, such as dementia, are not always well understood by breast cancer HCPs.ConclusionsThese results indicate that there are elements of age bias present amongst breast cancer HCPs. The study's findings of age-based assumptions and a poorer understanding of conditions which disproportionately affect older patients align with patterns of differential treatment towards older breast cancer patients suggesting that age bias may be, at least in part, driving differential treatment.     

The impact of age on outcome in early-stage breast cancer

Multiple studies have shown that breast-conserving therapy (BCT) and mastectomy have equivalent outcomes for large populations of women with early-stage breast cancer. For individual treatment decisions, however, it is important to appreciate the heterogeneity of disease. Recent molecular studies have suggested that "breast cancer" includes biologically distinct classes of disease; although these molecular distinctions are important, other patient-related factors also affect outcome and influence prognosis. One of the most important of these patient factors is the age of the patient at diagnosis. Numerous studies have shown very different breast cancer outcomes based on patient age; younger women typically have more aggressive tumors that are more likely to recur both locoregionally and distantly, and older women more commonly have less aggressive disease. The overall disease-specific outcomes, techniques, and doses for adjuvant radiation therapy and toxicity of treatments should be discussed within the context of age because breast cancer is a very different disease based on this factor. Arguments can be made that more aggressive locoregional therapy is warranted in populations of young women with breast cancer and perhaps less aggressive therapy in the elderly.     

Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast: a critical review of the literature.

PURPOSE: Patients younger than 35 to 45 years old at the time of diagnosis of invasive breast cancer have been found to have a worse prognosis than older patients in many studies. However, the impact of patient age at diagnosis on the outcome of treatment with either lumpectomy and radiation therapy (RT) or mastectomy for patients with ductal carcinoma-in-situ (DCIS) of the breast has not been extensively analyzed. MATERIALS AND METHODS: Articles addressing the effect of patient age at diagnosis on the outcome of treatment of DCIS with lumpectomy and RT or mastectomy were identified through the MEDLINE and CancerLit databases and reference lists of relevant articles. Studies were reviewed to determine the impact of patient age at diagnosis on clinical and pathologic features of DCIS, the influence of age on outcome after lumpectomy and RT, and the impact of age on outcome after mastectomy. RESULTS: DCIS in younger patients more frequently contains adverse prognostic pathologic factors and extends over a greater distance in the breast than in older patients. In series with adequate follow-up, younger patients treated with lumpectomy and RT had a significantly higher rate of local recurrence than older patients, especially for invasive local recurrences. Some studies have suggested that careful attention to margin status and excising larger volumes of tissue can reduce this difference substantially. No available data show that younger patients have better long-term cancer-free survival rates if treated by mastectomy rather than lumpectomy and RT. CONCLUSION: Successful treatment of younger patients with DCIS with lumpectomy and RT requires careful attention to patient evaluation, selection, and surgical technique. When this is done, age at diagnosis should not be a contraindication to breast-conserving therapy.     

Prognosis of younger and older patients with early breast cancer.

The use of mammography in recent years has resulted in an increase in the detection of small breast cancers. The beneficial effects of early detection on breast cancer mortality seem to differ with age. To obtain more insight into this matter we studied the long-term prognosis of patients with early invasive breast cancers (T1) in three age groups: 144 patients of age 40-49, 402 patients of age 50-69 and 192 patients 70 years or older at diagnosis. In all age groups, patients with a tumour of 1 cm or less have a longer breast cancer specific survival than patients with a tumour larger than 2 cm. The survival advantage in the case of tumours of a size rounded to 1.5 cm compared with tumours larger than 2 cm in the under age 50 group was marginal (and not significant). However, older patients with tumours of this size do have a significantly improved survival. It is more difficult to improve survival in younger patients through early detection, partly because of an apparent early metastatic potential of their tumours. A reduction in breast cancer mortality might be expected in women younger than 50 years of age only if a substantial proportion of the invasive cancers are detected before their size exceeds 1 cm.     

Breast Cancer in Young Women from a Low Risk Population in Nepal

Background: The overall incidence of breast cancer in South Asian countries, including Nepal, is low comparedto Western countries. However, the incidence of breast cancer among young women is relatively high. Breastcancer in such cases is characterized by a relatively unfavorable prognosis and unusual pathological features.The aim of this study was to investigate clinico-pathological and biological characteristics in younger breastcancer patients (<40 years) and compare these with their older counterparts. Materials and Methods: Ninehundred and forty four consecutive female breast cancer patients, admitted to the Department of Surgery,Tribhuvan University Teaching Hospital, Kathmandu, Nepal between November 1997 and October 2012, wereretrospectively analyzed. Results: Out of the 944 female breast cancer patients, 263 (27.9%) were <40 years. Themean age was 34.6±5.0 years among younger patients compared to 54.1±9.9 for those ≥40 years. The mean age atmenarche was also significantly lower (13.5±1.5 vs 14.2±1.5 years p=0.001) while the mean duration of symptomswas significantly longer (7.6 vs 6.5 months p=0.004). Family history of breast cancer was evident in 3.0% of theyoung women versus 0.3% in the older one. Mammography was performed less frequently in younger patients(59.7%), compared to older (74.4%), and was of diagnostic benefit in only 20% of younger patients compared to85% of older ones. At diagnosis, the mean tumor diameter was significantly larger in young women (5.0±2.5 vs4.5±2.4cm, p=0.005). Axillary lymph nodes were positive in 73% of younger patients and 59% of older patients.In the younger group, the proportion of stage III or IV disease was higher (55.1% vs 47.1%, p≤0.05). Theproportion of breast conserving surgery was higher in young patients (25.1% vs 8.7%) and a higher proportionof younger patients receive neoadjuvant chemotherapy (9.9% vs 2.8%). The most common histological type wasductal carcinoma (93.1% vs 86%). The proportion of histological grade II or III was higher in younger patients(55.9% vs 24.5%). Similarly, in the younger group, lymphatic and vascular invasion was more common (63.2%vs 34.3% and 39.8% vs 25.4%, respectively). Patients in the younger age group exhibited lower estrogen and/or progesterone receptor positivity (34.7% vs 49.8%). Although statistically not significant, the proportion oftriple negative tumors in younger age group was higher (22.4% vs 13.6%). Conclusions: Breast cancer in youngNepalese women represents over one quarter of all female breast cancers, many being diagnosed at an advancedstage. Tumors in young women exhibit more aggressive biological features. Hence, breast cancer in young womenis worth special attention for earlier detection.     

Is “Geriatric” Assessment Just for Older Patients?

Geriatric assessment (GA) is used in oncology to identify deficits in older patients with cancer that may affect treatment choice. We examine GA in 550 patients with early breast cancer, including both younger (<65 years) and older women (aged 65 years or older), to assess the potential value of this tool in younger, presumed “healthier” patients. Although older women have more GA-identified deficits overall, younger patients are more anxious. Suboptimal physical function was problematic across the age spectrum. GA domains can identify major deficits in younger patients beyond those likely to be uncovered in routine investigation.     

Breast-cancer early detection in low-income and middle-income countries: do what you can versus one size fits all

In general, rates of breast cancer are lower in low-income and middle-income countries (LMCs) than they are in more industrialised countries of North America and Europe. This lower incidence means that screening programmes aimed at early detection in asymptomatic women would have a lower yield--ie, substantially more women would need to be examined to find a true case of breast cancer. Because the average age of breast cancer is generally younger in LMCs, it has been suggested that breast-cancer screening programmes begin at an earlier age in these settings. However, the younger average age of breast cancer is mainly driven by the age distribution of the population, and fewer older women with breast cancer, rather than by higher age-specific incidence rates in younger women. Resources in LMCs might be better used to raise awareness and encourage more women with palpable breast lumps to seek and receive treatment in a timely manner.     

Stage and treatment variation with age in postmenopausal women with breast cancer: compliance with guidelines

Breast cancer-specific mortality is static in older women despite having fallen in younger age groups, possibly due to lack of screening and differences in treatment. This study compared stage and treatment between two cohorts of postmenopausal women (55-69 vs >70 years) in a single cancer network over 6 months. A total of 378 patients were studied (>70: N=167, 55-69 years: N=210). Older women presented with more advanced disease (>70: metastatic/locally advanced 12%, 55-69 years: 3%, P<0.01). Those with operable cancer had a worse prognosis (Nottingham Prognostic Index (NPI) >70: median NPI 4.4, 55-69 years: 4.25, P<0.03). These stage differences were partially explained by higher screening rates in the younger cohort. Primary endocrine therapy was used in 42% of older patients compared with 3% in the younger group (P<0.001). Older women with cancers suitable for breast conservation were more likely to choose mastectomy (>70: 57.5% mastectomy rate vs 55-69 years: 20.6%, P<0.01). Nodal surgery was less frequent in older patients (>70: 6.7% no nodal surgery, 55-69 years: 0.5%, P<0.01) and was more likely to be inadequate (>70: 10.7% <4 nodes excised, 55-69 years: 3.4%, P<0.02). In summary, older women presented with more advanced breast cancer, than younger postmenopausal women and were treated less comprehensively.     

Age at diagnosis in women with non-metastatic breast cancer: Is it related to prognosis?

ObjectivePrimary objective was to verify whether breast cancer patients aged less than 40 years at diagnosis have poorer prognosis than older patients. Secondary to assess prognostic factors influencing disease free survival.Methods941 women were diagnosed with non-metastatic breast cancer at NCI, Cairo in 2003. Epidemiologic, clinico-pathological characteristics, treatment modalities and disease free survival were compared among the two age groups. Prognostic factors were evaluated for association with disease-free survival.ResultsOne hundred-eighty-one patients (19.2%) were younger than 40 years and 760 (80.8%) were older. Older women presented with higher rates of comorbidities and younger women presented with more hormone non-responsive tumors. Young women presented with larger tumors pT4 = 13.8% compared to 8.6% in older women, yet not significant. Young women were treated with more conservative surgery, more adjuvant chemotherapy and radiotherapy while older women with more radical mastectomies and more hormonal treatment. Recurrence rates were significantly higher among young women 44.2% compared to 34.5% in older women. Five year disease free survival in young women was 38.9% ± 4.6% compared to 48.6% ± 2.5% with adjusted hazard ratio of 1.22 95% CI (0.91–1.64), p = 0.19. Multivariate analyses identified positive axillary lymph nodes (pN2-pN3), larger tumor size (pT3-pT4), hypertension, lobular carcinoma type and lack of adjuvant systemic treatment as independent factors associated with poor DFS.ConclusionYoung women were not found to have poorer prognosis, yet they presented with more ER negative tumors. Most of women presented with advanced stage and young women had higher recurrence rates.     

Oncobiology and treatment of breast cancer in young women

Female breast cancer emerged as the leading cancer type in terms of incidence globally in 2020. Although mortality due to breast cancer has improved during the past three decades in many countries, this trend has reversed in women less than 40 years since the past decade. From the biological standpoint, there is consensus among experts regarding the clinically relevant definition of breast cancer in young women (BCYW), with an age cut-off of 40 years. The idea that breast cancer is an aging disease has apparently broken in the case of BCYW due to the young onset and an overall poor outcome of BCYW patients. In general, younger patients exhibit a worse prognosis than older pre- and postmenopausal patients due to the aggressive nature of cancer subtypes, a high percentage of cases with advanced stages at diagnosis, and a high risk of relapse and death in younger patients. Because of clinically and biologically unique features of BCYW, it is suspected to represent a distinct biologic entity. It is unclear why BCYW is more aggressive and has an inferior prognosis with factors that contribute to increased incidence. However, unique developmental features, adiposity and immune components of the mammary gland, hormonal interplay and crosstalk with growth factors, and a host of intrinsic and extrinsic risk factors and cellular regulatory interactions are considered to be the major contributing factors. In the present article, we discuss the status of BCYW oncobiology, therapeutic interventions and considerations, current limitations in fully understanding the basis and underlying cause(s) of BCYW, understudied areas of BCYW research, and postulated advances in the coming years for the field.