Patterns of toxicity in older patients with breast cancer receiving adjuvant chemotherapy

Summary Objective. To retrospectively determine the relationship of age to toxicity from adjuvant chemotherapy for breast cancer.Design and Methods We identified 1405 consecutive patients age 65 or older with primary invasive breast cancer who were seen at Memorial Sloan-Kettering Cancer Center from January 1998 to December 2000. Patients selected from this cohort for analysis were aged 65 or older at diagnosis; received their follow-up care at Memorial Sloan-Kettering Cancer Center; had stage I, II, or III breast cancer; and received adjuvant chemotherapy consisting of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), an anthracycline-based regimen (AC [doxorubicin and cyclophosphamide], or AC-T [AC and paclitaxel or docetaxel]). Exclusion criteria included prior chemotherapy or previous breast cancer. Results. One hundred thirty-two patients were included in this study, with a mean age of 70 (range 65–79). Comorbidity measured by the Charlson comorbidity index was low: score 0 (83%), 1 (12%), 2 (5%); with stages: I(18%), IIA (41%), IIB (27%), IIIA (8%), IIIB (6%), T1Nx (1%). Patients receiving an anthracycline-based regimen were more likely to experience grade 3 or 4 toxicity (p=0. 01), require hospitalization (p<0.001), and/or develop febrile neutropenia (p<0.001). Treatment delays due to myelosuppression occurred more frequently in patients receiving CMF (p<0.001). The type of chemotherapy regimen (anthracycline compared to CMF) was a better predictor for toxicity than increased age or comorbidity score. Conclusions. In this cohort of older patients with breast cancer, the risk for toxicity from adjuvant chemotherapy depended more on the type of regimen (anthracycline vs. CMF) than the patient’s chronological age.     

What threshold for adjuvant therapy in older breast cancer patients?

PURPOSE: To consider the question of when to prescribe adjuvant treatment for elderly breast cancer patients, particularly when comorbidities are present. Knowledge of the threshold relapse risks above which adjuvant treatment is worth prescribing would enhance decision making. PATIENTS AND METHODS: A Markov analysis of data from the medical literature was conducted. Patients aged 65 to 85 years were considered, along with three levels of comorbidity. The threshold risk of relapse at 10 years (RR10), at which time treatment provides absolute reduction or reduction of an absolute 1% in relapse or mortality, was evaluated. RESULTS: The threshold RR10 for an absolute reduction in mortality risk by adjuvant treatment was low through the age of 85 years. However, for an absolute 1% reduction, the effect of treatment on relapse and the effect of treatment on mortality increasingly diverged. The threshold RR10 for an absolute 1% reduction in relapse risk remained fairly low (5% to 6% for tamoxifen, 12% to 19% for chemotherapy). The threshold RR10 for an absolute 1% reduction in mortality risk, although starting close to the RR10 for an absolute 1% reduction in relapse risk, rose sharply. For tamoxifen, the difference between the two was 4% for an average 65-year-old, 6% at the age of 75 years, and 15% at the age of 85 years. For chemotherapy, the differences were 6%, 12%, and 30%, respectively. Similarly, thresholds increased with increasing comorbidity. In older and sicker patients, the maximum benefit was reached after 5 years rather than 10 years. CONCLUSION: Older breast cancer patients can expect a reduction in relapse that is fairly similar to that of younger patients. However, the effect on mortality diverges markedly, and attention should be paid to this difference in clinical decision making. Comorbidity should be considered in recommendations for adjuvant treatment, including clinical practice guidelines.     

Patient characteristics and health system factors associated with adjuvant radiation therapy receipt in older women with early-stage endometrial cancer

IntroductionAmong women with early-stage endometrial cancer (EC), age, stage, grade, and histology are used to determine fitness for adjuvant radiation therapy (RT) administration. We examined non-cancer factors associated with adjuvant RT receipt in older women with early-stage EC.Materials & methodsUsing data from the Surveillance Epidemiology and End Results cancer registry program linked with Medicare claims, we identified 25,654 women (aged ≥66 years) diagnosed with first primary stage I-II EC during 2004–2017 who underwent a hysterectomy. Diagnosis and procedure codes were used to identify adjuvant RT claims filed for the seven-month period post-hysterectomy. Multivariable log-binomial regression was used to estimate adjuvant RT prevalence associated with patient characteristics and health system factors after adjustment for age, frailty, and endometrial factors.ResultsAdjuvant RT was less commonly administered to Asian American and Pacific Islander patients than non-Hispanic White patients (Prevalence ratio [PR], 0.84; 95% confidence interval [CI], 0.73 to 0.97). Compared to women treated in the Northeast region, women treated other regions of the US were less likely to undergo adjuvant RT (PR, 0.75; 95% CI, 0.71 to 0.79). Residing in rural or high neighborhood-poverty counties was associated with lower adjuvant RT administration. Higher comorbidity score was not associated with reduced prevalence of adjuvant RT receipt; however, women with high probability of predicted probability of frailty were less likely to undergo adjuvant RT (PR, 0.67; 95% CI, 0.55 to 0.81) compared to women with low probability of frailty. Women who received lymph node assessment were more likely to undergo adjuvant RT compared to women who did not (PR, 1.43; 95% CI, 1.34 to 1.51). Women treated by a gynecologic oncologist were more likely to undergo adjuvant RT compared to women treated by a non-gynecologic oncologist (PR 1.09; 95% CI, 1.04 to 1.14). Adjuvant RT was more commonly administered to women treated in larger academic hospitals.DiscussionFindings suggest that various non-cancer factors affect the delivery of adjuvant RT to older women with early-stage EC in real-world oncology practice. Advancing our understanding of factors associated with adjuvant RT administration may help expand equitable access to RT.     

Patterns of axillary metastases in breast cancer

Thirty-seven (4.1%) cases of nodal metastases skipping the first level are reported in a consecutive series of 912 breast cancer axillary dissections including 392 N+ cases. First level nodes examination is sufficiently accurate in assessing the quality of nodal status (negative or positive) but not the extent of nodal involvement (number of involved nodes).     

乳腺癌伴腋窝淋巴结转移术后放射治疗研究(附78例≥8个淋巴结转移的乳腺癌临床观察)

目的　探讨放射治疗对腋窝淋巴结转移数≥8 个、T1 ～3 期乳腺癌的作用。方法　回顾性分析78 例行根治术的浸润性乳腺癌。术后均接受辅助化疗,疗程0.5 ～4.0 个;38 例兼接受了术后放射治疗,放射治疗部位为同侧锁骨上、下及内乳淋巴引流区,且29 例加胸壁、25 例加腋窝,放射治疗剂量45 Gy 以上占89.5 % 。结果　放射治疗组和未放射治疗组的5 年局部复发率分别为30 .8%和57.4 %( P= 0.010) ;5 年无瘤生存率分别为47 .7% 和15.7% ( P= 0 .002) ;5 年总生存率分别为64.4% 和40.6% (P= 0.083) 。做和未做胸壁足量放射治疗的胸壁复发率为7 .7 % (2/26) 和3/9 (P<0 .05)。做和未做腋窝放射治疗的腋窝复发率为4 .0% (1/25)和7 .7 % (1/13)(P> 0.05)。结论　对腋窝淋巴结转移数≥8 个、T1～3 期乳腺癌,除术后化疗外,应常规行术后放射治疗,胸壁应列为常规的照射部位之一,腋窝可不必照射     

Bilateral primary breast cancer in patients treated with adjuvant therapy

Between 1974 and 1986, 1036 patients with operable breast cancer were treated with doxorubicin-containing combination chemotherapy regimens. Of these, 44 patients had bilateral breast cancer prior to initiation of adjuvant therapy (prechemotherapy) and 17 patients developed primary breast cancer on the contralateral side during or after completion of adjuvant therapy (postchemotherapy). The objectives of the study were twofold: to determine the incidence of bilateral primary breast cancer and to determine the effect of second primary breast cancer on prognosis of patients treated for disease in the contralateral breast. The estimated disease-free and overall survival of patients with prechemotherapy bilateral disease was similar to the patients with unilateral breast cancer. Four hundred eight patients received tamoxifen in addition to combination chemotherapy during adjuvant therapy. The incidence of contralateral breast cancer at 2 years in patients treated with tamoxifen was 0.4% in comparison to 0.8% in patients treated with chemotherapy alone. Time to development of second breast cancer in patients treated with or without tamoxifen was not significantly different (p = 0.41). We conclude that patients with bilateral breast cancer have a prognosis similar to that of patients with comparably staged unilateral disease. Although the rate of bilateral disease observed among patients treated with adjuvant chemotherapy and tamoxifen was somewhat lower than for those receiving chemotherapy only, the difference was not statistically significant.     

Socioeconomic factors associated with adjuvant hormone therapy use in older breast cancer survivors

BACKGROUND:

The authors sought to identify socioeconomic (SES) factors associated with adjuvant hormone therapy (HT) use among a contemporary population of older breast cancer survivors.

METHODS:

Telephone surveys were conducted among women (ages 65‐89 years) residing in 4 states (California, Florida, Illinois, and New York) who underwent initial breast cancer surgery in 2003. Demographic, SES, and treatment information was collected.

RESULTS:

Of 2191 women, 67% received adjuvant HT with either tamoxifen or an aromatase inhibitor (AI); 71% of those women were on an AI. When adjusting for multiple demographic and SES factors, predictors of HT use were better education (high school degree or higher), better informational/emotional support, and younger age (ages 65‐79 years). Race/ethnicity, income, and insurance coverage for medication costs were not associated with receiving HT. For those on HT, when adjusting for all other factors, women were more likely to receive an AI if they had insurance coverage for some or all medication costs, if they were wealthier, if they had better informational/emotional support, and if they were younger (ages 65‐69 years).

CONCLUSIONS:

The majority of older women in this population‐based cohort received adjuvant HT, and the adoption of AIs was early. The results indicted that providers should be aware that a woman's education level and support system influence her decision to take HT. Given the high cost of AIs, their benefits in postmenopausal women with hormone receptor‐positive breast cancer, and the current finding that women with no insurance coverage for medication costs were significantly less likely to receive an AI, we recommend that policymakers address this issue. Cancer 2011. © 2010 American Cancer Society.     

Postmastectomy radiotherapy and concomitant adjuvant chemotherapy versus adjuvant chemotherapy alone in premenopausal breast cancer patients with positive axillary nodes

AIMS: To evaluate the efficacy of postmastectomy radiotherapy (RT) combined with adjuvant chemotherapy compared to adjuvant chemotherapy alone as regards overall survival (OS), overall disease-free survival (ODFS), local disease-free survival (LDFS) and distant disease-free survival (DDFS). METHODS: We reviewed retrospectively two non-randomized groups of premenopausal high-risk breast cancer patients treated from 1985 to 1990 in the following Institutions: Department of Radiation Oncology of Brescia University, "Istituto del Radio O. Alberti" (IRA), and Department of Oncology of Brescia Hospital "Beretta Foundation" (BF). A total of 163 patients was found to satisfy the criteria of the current analysis: 81 patients received adjuvant chemotherapy alone [6 cycles CMF(1-8)] at BF and 82 patients received postoperative radiotherapy and chemotherapy [8 cycles CMF(1-21)] at IRA. A modified CMF schedule was chosen at IRA to avoid the feared increase in toxicity due to the association with RT. Primary surgical treatment was modified radical mastectomy with axillary node dissection in both cases. RESULTS: A statistically significant improvement in OS was found in systemic adjuvant therapy patients compared to those also given RT (77.6% vs 59%; P = 0.0025). No statistically significant improvement in ODFS was found in the CMF(1-8) arm compared to the RT and CMF(1-21) stm: 51.6% vs 43.6%; P = 0.46. A statistically significant improvement in LDFS at 5 years was found in irradiated patients (89.3% vs 76.2%; P <0.05). The DDFS was also improved, although without evidence of statistical significance, in the CMF(1-8) group: at 5 years 65% vs 44% (P = 0.059). CONCLUSIONS: The study confirmed that RT reduces the risk of local recurrence but without a statistically significant reduction in mortality. The lack of a survival benefit may somehow reflect the dose reduction in CMF(1-21). The evidence that CMF(1-8) offers undoubtable advantages over the CMF(1-21) regimen in OS and, perhaps, in distant control suggests that the dose intensity of CMF in this setting may also be important. In fact, although many CMF(1-8) patients received a dose intensity lower than 100%, 95% of them received a dose intensity higher than the maximum one of the CMF(1-21) patients. Although our results should be interpreted with caution, they seem to provide further rationale for testing the association of postoperative radiotherapy and the CMF(1-8) regimen in stage II breast cancer with positive nodes and treated with demolitive surgery, as already done in the conservative management of breast cancer, also in view of the new support therapies now available (i.e. hematologic growth factors).     

Targeted therapy for breast cancer in older patients

Older patients are one of the most relevant sub-groups of patients with breast cancer and will only gain in importance as demographic transition unfolds. Their management, in both the early and advanced settings, should take into consideration specific clinical needs and is made more difficult by the limited availability of evidence on the efficacy and safety of standard treatment regimens in older patients. At the root of this situation is the low rate of participation of older patients in clinical trials, often due to age limits for inclusion, and limitations on the participation of persons with significant comorbidities or organ dysfunction. Although this has begun to change in recent years, most agents currently in use have not been tested in a substantial number of older patients. This includes the targeted agents that have, in the last fifteen years, changed the prognosis of patients with early and advanced breast cancer. Most data guiding the use of targeted agents in older patients come from sub-analysis of larger trials or small retrospective cohort studies. The goal of this review is to go over the available evidence regarding the efficacy and safety of targeted agents approved for use in breast cancer (trastuzumab, lapatinib, T-DM1, pertuzumab, neratinib, palbociclib, bevacizumab, ribociclib, abemaciclib, everolimus, olaparib, talazoparib), and place their side effects into an older-specific context in order to help medical oncologists when making treatment decisions and managing older patients with breast cancer.     

Routine cardiac evaluation in patients with early-stage breast cancer before adjuvant chemotherapy

IntroductionThis population-based study of women diagnosed with early-stage breast cancer aimed to (i) determine the current utilization pattern of multigated acquisition (MUGA) scans before adjuvant chemotherapy (AdjC) treatment, and (ii) examine the impact of MUGA scan results on AdjC decision making.MethodsAll women who underwent curative-intent surgery for stage I-III breast cancer between October 2005 and September 2006 in Nova Scotia, Canada, were identified through the provincial cancer registry. A retrospective chart review was performed to abstract all relevant clinical-pathologic variables, including baseline cardiac risk factors. The association between MUGA scan utilization and clinical-pathologic variables, as well as receipt and type of AdjC, was examined through univariate and multivariate analyses.ResultsThe study included 593 women, of whom 238 (40%) received AdjC (94% anthracycline vs. 6% nonanthracycline) and 198 (33%) underwent baseline MUGA scans. Of those received AdjC, 80% underwent MUGA scans. MUGA scan utilization was associated with AdjC treatment (yes vs. no; P < .0001), Her-2/neu status (positive vs. negative vs. not tested; P < .0001), and AdjC regimen (anthracycline vs. nonanthracycline; P < .0001). Abnormal MUGA results were observed in 5 (2.5%) of 198; all were smokers, and 4 were >65 years of age. In the 1 patient <50 years old, subsequent echocardiograms indicated normal cardiac function.ConclusionsRoutine baseline MUGA scans before AdjC were abnormal and changed the AdjC treatment decision in only 2.5% and 2.0% of patients, respectively. Routine MUGA scans before anthracycline-based AdjC without trastuzumab, however, did not influence AdjC decisions for younger patients <65 years of age without underlying cardiac risk factors.     

淋巴结阴性乳腺癌患者辅助治疗的研究进展

淋巴结阴性乳腺癌患者中有20%～30%经手术治疗后复发和转移.本文综述了如何选择需要内分泌治疗和/或化疗的淋巴结阴性乳腺癌患者,以及如何选择正确的治疗模式.     

Patterns of axillary staging and management in clinically node positive breast cancer patients treated with neoadjuvant systemic therapy: Results of a survey amongst breast cancer specialists

IntroductionVarious options for axillary staging after neoadjuvant systemic therapy (NST) are available for breast cancer patients with a clinically positive axillary node (cN+). This survey assessed current practices amongst breast cancer specialists.Materials and methodsA survey was performed amongst members of the European Society of Surgical Oncology and two UK-based Associations: the Association of Breast Surgery and the British Association of Surgical Oncology. The survey included 3 parts: 1. general information, 2. diagnostic work-up and 3. axillary staging after NST.ResultsA total of 310 responses were collected: parts 1, 2 and 3 were fully completed by 282 (91%), 270 (87.1%) and 225 (72.6%) respondents respectively. After NST, 153/267 (57.3%) respondents currently perform ALND routinely and 114 (42.7%) respondents perform less invasive restaging of the axilla with possible omission of ALND. In the latter group, 85% does and 15% does not use nodal response seen on imaging to guide the axillary restaging procedure. Regarding respondents that do use imaging: 95% would perform a less invasive staging procedure in case of complete nodal response on imaging (63% sentinel lymph node biopsy (SLNB), excision of a previously marked positive node with SLNB (21%) and without SLNB (11%)). In case of no nodal response on imaging 77% would perform ALND.ConclusionCurrent axillary staging and management practices in cN + patients after NST vary widely. To determine optimal axillary staging and management in terms of quality of life and oncologic safety, breast specialists are encouraged to include patients in clinical trials/prospective registries.     

Targeted adjuvant therapy in breast cancer

Introduction: The potential of molecular targeted therapy to improve the clinical outcomes of patients with early-stage breast cancer (BC) as adjuvant therapy has been first demonstrated through endocrine treatment. The introduction of HER2 blockade, through the successful clinical development of trastuzumab, changed the natural history of HER2-positive BC subtype.

Areas covered: There are ongoing efforts to augment further the use of targeted agents as adjuvant treatment in BC, hoping that early introduction of targeted therapy blocking key oncogenic drivers of micro-residual disease, will significantly improve clinical outcomes. In the present Review, we present data through extensive search of PubMed about the following targeted adjuvant therapeutic strategies in BC: i) HER2 blockade and ongoing efforts to further augment its efficacy for patients with HER2-positive disease, ii) angiogenesis inhibition, iii) PI3K-mTOR- AKT pathway inhibition, iv) CDK4/6 inhibition, v) PARP inhibition.

Expert commentary: we provide insights about challenges and potential ways to overcome them, in terms of successful clinical development of targeted agents as adjuvant therapy for patients with BC. In particular, we emphasize the need to systematically assess minimal residual cancer burden as a way to increase the rates of successful clinical development of targeted agents in the adjuvant setting.