Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: A large cohort study from clinical practice

Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006–2009). DFS and OS were estimated using the Kaplan–Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40–69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.     

Advanced topics in evidence-based urologic oncology: surrogate endpoints

Clinical trials often report surrogate endpoint data. A surrogate endpoint is a biological marker or clinical sign that can be substituted for a patient-important outcome. Using surrogate endpoints correctly may facilitate and expedite clinical trials and may improve medical decisions. However, rigorous criteria must be met for an endpoint to be considered a valid surrogate. The purpose of this article is to review the topic of surrogate endpoints in the context of a urologic encounter.     

Progression-free survival and quality of life in metastatic breast cancer: The patient perspective

IntroductionTreatment advances for metastatic breast cancer (mBC) have improved overall survival (OS) in some mBC subtypes; however, there remains no cure for mBC. Considering the use of progression-free survival (PFS) and other surrogate endpoints in clinical trials, we must understand patient perspectives on measures used to assess treatment efficacy.ObjectiveTo explore global patient perceptions of the concept of PFS and its potential relation to quality of life (QoL).Materials and methodsVirtual roundtables in Europe and the United States and interviews in Japan with breast cancer patients, patient advocates, and thought leaders. Discussions were recorded, transcribed, and analyzed thematically.ResultsLengthened OS combined with no worsening or improvement in QoL remain the most important endpoints for mBC patients. Time when the disease is not progressing is meaningful to patients when coupled with improvements in QoL and no added treatment toxicity. Clinical terminology such as “PFS” is not well understood, and participants underscored the need for patient-friendly terminology to better illustrate the concept. Facets of care that patients with mBC value and that may be related to PFS include relief from cancer-related symptoms and treatment-related toxicities as well as the ability to pursue personal goals. Improved communication between patients and providers on managing treatment-related toxicities and addressing psychosocial challenges to maintain desired QoL is needed.ConclusionWhile OS and QoL are considered the most relevant endpoints, patients also value periods of time without disease progression. Incorporation of these considerations into the design and conduct of future clinical trials in mBC, as well as HTA and reimbursement decision-making, is needed to better capture the potential value of a therapeutic innovation.     

Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: a systematic review and meta-analysis

Purpose

To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer.

Methods

Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity.

Results

Five trials were identified with 515 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI: 1.39–2.46; p-value < 0.001). No significant difference in terms of breast-conserving surgery between the two treatment arms was observed (OR: 0.98, 95% CI: 0.80–1.19, p-value = 0.82). Regarding toxicity, the addition of trastuzumab did not increase the incidence of neutropenia, neutropenic fever, and cardiac adverse events.

Conclusion

The addition of trastuzumab in HER2-positive breast cancer in the neoadjuvant setting improves the probability of achieving higher pCR with no additional toxicity. Based on the available evidence, the use of trastuzumab combined with neoadjuvant chemothetherapy in patients with HER2-positive breast cancer seems to offer substantial benefit in terms of pCR.     

Pathologic stage as a surrogate for oncologic outcomes after receipt of neoadjuvant chemotherapy for high-grade upper tract urothelial carcinoma

ObjectiveWhether pathologic stage at radical nephroureterectomy (RNU) can serve as an appropriate surrogate for oncologic outcomes in patients with high-grade (HG) upper tract urothelial carcinoma (UTUC) treated with neoadjuvant chemotherapy (NAC) is not defined. We sought to determine whether patients who achieve pathologically non-muscle-invasive (ypT0, ypTa, ypT1, ypTis) HG UTUC after receipt of NAC exhibit oncologic outcomes comparable to those who are inherently low stage without chemotherapy.MethodsWe identified 647 UTUC patients who underwent RNU among 3 institutions from 1993to2016. Patients with low or unknown grade, pathologic muscle invasion, or receipt of adjuvant chemotherapy were excluded. We compared clinicopathologic data and oncologic outcomes between pT0-1 and ypT0-1 patients. Kaplan-Meier analysis was used to assess overall (OS), cancer-specific (CSS), and systemic recurrence-free (RFS) survival. Predictors of these endpoints were identified using Cox regression.Results234 (43 ypT0-1, 191 pT0-1) patients with HG UTUC were included. Two patients exhibited pathologic complete response after NAC. OS (P = 0.055), CSS (P = 0.152), and RFS (P = 0.098) were similar between ypT0-1 and pT0-1 patients. Predictors of worse outcomes included African-American race (RFS, CSS, and OS), Charlson score (OS), and systemic recurrence (OS and CSS).ConclusionsPatients with HG UTUC who achieve ypT0-1 stage after NAC exhibit favorable oncologic outcomes comparable to those inherently non-muscle-invasive who do not receive chemotherapy. Improvements in clinical staging will play an important role in better defining candidacy for NAC in treating HG UTUC while minimizing overtreatment. Furthermore, pathologic stage may serve as an appropriate early surrogate for oncologic endpoints in designing clinical trials.     

Moment of truth-adding carboplatin to neoadjuvant/adjuvant chemotherapy in triple negative breast cancer improves overall survival: An individual participant data and trial-level Meta-analysis

ImportanceCarboplatin increases the pathological complete remission (pCR) rate in triple negative breast cancer (TNBC) when added to neoadjuvant chemotherapy, however, evidence on its effect on survival outcomes is controversial.MethodsThe study was prospectively registered at PROSPERO (CRD42021228386).We systematically searched PubMed, Embase, Cochrane Central Register of Clinical Trials, and conference proceedings from January 1, 2004 to January 30, 2022 for relevant randomized clinical trials (RCTs) of (neo)adjuvant chemotherapy in TNBC patients, with carboplatin in the intervention arm and standard anthracycline taxane (AT) in the control arm. PRISMA guidelines were used for this review. Data were pooled using fixed and random effects models as appropriate on extracted hazard ratios (HR). Individual patient data (IPD)for disease free survival (DFS) and overall survival (OS) were extracted from published survival curves of included RCTs; DFS and OS curves for each trial and the combined population were reconstructed, and HR estimated. The primary outcome was DFS; OS, pCR, and toxicity were secondary outcomes.ResultsEight trials with 2425 patients were included. Carboplatin improved DFS (HR 0.60; 95% CI 0.47 to 0.78; I² 45%, p < 0.001) compared with AT at trial level and IPD level (HR 0.66; 95%CI, 0.55 to 0.80, p < 0.001) analysis. The OS also improved with carboplatin at both trial level (HR 0.69, 95%CI 0.50 to 0.95, I² 41%, p = 0.02) and IPD level (HR 0.68; 95%CI, 0.54 to 0.87, p = 0.002) analysis. The pCR as expected, was better in the carboplatin arm (OR 2.11; 95% CI = 1.44–3.08; I² 67%, p = 0.009). Anaemia and thrombocytopaenia were higher in the carboplatin arm.Conclusionand relevance: Carboplatin added to (neo)adjuvant chemotherapy in TNBC improves survival, as shown in both trial level and IPD analysis.     

Oesophageal cancer: current status of multimodality therapy

Multimodality treatment options have been widely promoted in the therapy for locally advanced oesophageal cancer (cT3/4Nx). Generally neoadjuvant chemotherapy and combined radiochemotherapy are frequently used in this setting. The recent meta-analyses evaluating randomised trials of different neoadjuvant therapy protocols prior to surgery for patients with locally advanced oesophageal cancer showed only a modest improvement in survivial of 5-10% survival at 5 years. In contrast, the meta-analyses reveal that patients with excellent histopathological responses seem to highly benefit from neoadjuvant regimens. Patients with poor histopathological responses have no benefit but rather disadvantegeous prognoses. Therefore, predictive markers to allow individualisation of multimodality treatment in locally advanced esophageal cancer are urgently needed.     

Neoadjuvant endocrine treatment in primary breast cancer – Review of literature

Chemotherapeutic agents have dominated neoadjuvant treatment compared to endocrine agents in the past and have demonstrated their ability to produce tumour shrinkage to allow breast conservation. However, in the more recent setting, studies have been emerging with the use of aromatase inhibitors, especially comparing its use with tamoxifen in selected group of patients.The role of tamoxifen in its ability to achieve tumour shrinkage has been evaluated in the past, and has shown to produce slow but sustained response. Aromatase inhibitors have shown superiority over tamoxifen in adjuvant and metastatic setting, and the aim of our study was to compare their outcome with regard to response and breast conservation in the neoadjuvant setting. We also looked into optimum duration of neoadjuvant treatment and also the role of pathological complete response as a surrogate marker for clinical outcome.Our review highlights the superiority of aromatase inhibitors over tamoxifen in the neoadjuvant setting and even challenges chemotherapy with regard to response in selected group of patients.     

Review of the development of letrozole and its use in advanced breast cancer and in the neoadjuvant setting

Five years of adjuvant endocrine therapy with the antiestrogen tamoxifen has been shown to significantly reduce the risk of recurrence in women with early breast cancer and has thus been the standard of adjuvant therapy for this malignancy over the last two decades. Tamoxifen has also been used for the first-line treatment of advanced or metastatic breast cancer, and it was studied in the neoadjuvant setting to promote breast-conserving surgery in those patients who may be otherwise ineligible. However, comparative clinical trials involving the more recently approved third-generation aromatase inhibitor drugs (anastrozole, letrozole, and exemestane) have challenged tamoxifen as first-line therapy in advanced/metastatic breast cancer as well as in the neoadjuvant setting. Although trials with other AIs have shown improved efficacy and better tolerability over tamoxifen, letrozole has consistently demonstrated superiority over tamoxifen when used as first-line treatment for advanced/metastatic breast cancer or as neoadjuvant therapy. The efficacy of letrozole in the neoadjuvant setting further extends to those tumors with positive human epidermal growth factor receptor (HER1) and/or HER2 expression, which are often less responsive to tamoxifen. The encouraging results of such trials identify letrozole as a better alternative to tamoxifen in improving responses rates in the treatment of advanced breast cancer and as neoadjuvant therapy, which allows breast-conserving surgery in women with inoperable breast cancer or who were not candidates for breast-conserving surgery.     

Residual CIS after neoadjuvant chemotherapy and radical cystectomy for muscle invasive bladder cancer: Implications for neoadjuvant trials

PurposeTo better define surrogate endpoints for neoadjuvant chemotherapy (NAC) trials in patients with muscle-invasive bladder cancer. We compared survival in patients with carcinoma in-situ (CIS) only vs. complete response following NAC and radical cystectomy (RC).Materials and MethodsPatients with cT2-4N0M0 disease treated with NAC and RC between 2001 and 2018 were stratified by response: complete response (CR, pT0N0), partial response (PR, pTaN0, pT1N0+/-CIS), CIS-only (pTisN0), stable disease (SD, pT2N0), or progressive disease (PD, >pT2N0). Primary endpoints were overall survival (OS) and risk of recurrence in patients with CIS-only vs. CR. Multivariable Cox proportional hazards regression model was used for OS and a competing risks proportional hazards model was used for risk of recurrence.ResultsOf 1,406 patients in our institution cohort, 340 patients met inclusion criteria. Kaplan-Meier mean estimates of OS for CR and CIS-only were 108.9 months (95% CI 89.7–127.9) and 125.8 months (95% CI 112.3–139.3), respectively (P = 0.13). Cox proportional hazards model found no difference in OS between patients with PR (HR 1.06, 95% CI 0.33–2.58, P = 0.897) or CIS-only (HR 0.422, 95% CI 0.15–1.18, P = 0.101) when compared to CR. The risk of recurrence was similar between patients with CIS-only (HR 0.73, 95% 0.29–1.84, P = 0.49) and PR (HR 1.32, 95% CI 0.54–3.29, P = 0.54) when compared to CR on competing risks analysis.ConclusionsResidual CIS-only after NAC and RC demonstrated similar survival outcomes when compared to patients with pathologic CR. Further study in large multi-institutional cohorts may further validate CIS-only as an additional surrogate endpoint after NAC and may inform future trials.     

Issues with the Use of Prostate-Specific Antigen as a Surrogate End Point in Hormone-Resistant Prostate Cancer

ContextHigh demand for new drugs in cancer therapy has resulted in a drive to reduce the length of clinical trials. One way to achieve this is to use surrogate end points for overall survival (OS). Measurement of prostate-specific antigen (PSA) levels is widely used in screening for prostate cancer and may be used as a biomarker of disease progression. However, although PSA may serve as a suitable prognostic biomarker, its utility as a valid surrogate end point for OS in hormone-resistant prostate cancer (HRPC) trials has been inconclusive.Evidence acquisitionThe utility of PSA as a surrogate end point in HRPC is reviewed and alternative recommendations discussed. A nonsystematic review of the literature, including PubMed and congress abstracts, was performed in 2008.Evidence synthesisDespite being widely available and easy to measure, reductions in PSA levels have not been validated as a surrogate end point for use in clinical trials of agents with novel mechanisms of action. Conflicting data from preliminary studies of cytotoxic and molecular-targeted agents in HRPC have shown that improvements in OS are not consistently reflected by reductions in PSA. There are a number of potential reasons for this inconsistency, including heterogeneity of PSA expression with disease progression and the influence of comorbidities, including age. Although changes in PSA levels may be a suitable surrogate end point for studies of cytotoxic agents, it may have less utility in studies of targeted agents with antiproliferative or anti-invasive mechanisms of action. As questions have emerged about the utility of PSA levels as a surrogate end point, the Prostate Cancer Clinical Trials Working Group has reviewed the criteria for outcome measures in clinical trials that evaluate systemic treatment for patients with progressive prostate cancer. Recommendations note that PSA responses may be delayed in trials of noncytotoxic agents, and rising PSA levels in the absence of other signs of progression should not lead to discontinuation of trials.ConclusionsOS remains the most accurate end point for clinical trials, and changes in PSA levels may not reflect a patient's response to therapy.     

Novel Agents for Chemoprevention, Screening Methods, and Sampling Issues

An aggressive approach to breast cancer control based on preventing the disease must complement efforts at effective treatment. To date clinical trials testing new chemopreventative agents have not generally met with the kind of success expected. A wide range of new breast cancer chemopreventative agents are poised to be tested in clinical trials. We review these novel agents and approaches, including those for which clinical trials have been initiated and those that are promising in the preclinical arena. Further progress in this area requires not only new agents, but novel methods for screening for risk assessment, sampling and development of intermediate biomarkers. We review these novel potential surrogate endpoints, including new imaging techniques, breast sampling approaches, and methods to assess biomarkers in breast epithelium. Factors that could contribute to a meaningful choice of the chemopreventive agents and the design of clinical trials are discussed.     

Considerations for Development of Surrogate Endpoints for Antifracture Efficacy of New Treatments in Osteoporosis: A Perspective

Because of the broad availability of efficacious osteoporosis therapies, conduct of placebo‐controlled trials in subjects at high risk for fracture is becoming increasing difficult. Alternative trial designs include placebo‐controlled trials in patients at low risk for fracture or active comparator studies, both of which would require enormous sample sizes and associated financial resources. Another more attractive alternative is to develop and validate surrogate endpoints for fracture. In this perspective, we review the concept of surrogate endpoints as it has been developed in other fields of medicine and discuss how it could be applied in clinical trials of osteoporosis. We outline a stepwise approach and possible study designs to qualify a biomarker as a surrogate endpoint in osteoporosis and review the existing data for several potential surrogate endpoints to assess their success in meeting the proposed criteria. Finally, we suggest a research agenda needed to advance the development of biomarkers as surrogate endpoints for fracture in osteoporosis trials. To ensure optimal development and best use of biomarkers to accelerate drug development, continuous dialog among the health professionals, industry, and regulators is of paramount importance.     

The neoadjuvant rectal score and a novel magnetic resonance imaging based neoadjuvant rectal score are stage independent predictors of long-term outcome in locally advanced rectal cancer

Aim

Neoadjuvant rectal (NAR) score is an early surrogate for longer-term outcomes in rectal cancer undergoing radiotherapy and resection. In an era of increasing organ preservation, resection specimens are not always available to calculate the NAR score. Post-treatment magnetic resonance imaging (MRI) re-staging of regression is subjective, limiting reproducibility. We explored the potential for a novel MRI-based NAR score (mrNAR) adapted from the NAR formula.

Methods

Locally advanced rectal cancer patients undergoing neoadjuvant therapy (nCRT) and surgery were retrospectively identified between 2008 and 2020 in a single cancer network. mrNAR was calculated by adapting the NAR formula, replacing pathological (p) stages with post-nCRT MR stages (ymr). Cox regression assessed relationships between clinicopathological characteristics, NAR and mrNAR with overall survival (OS) and recurrence-free survival (RFS).

Results

In total, 381 NAR and 177 mrNAR scores were calculated. On univariate analysis NAR related to OS (hazard ratio [HR] 2.05, 95% confidence interval [CI] 1.33–3.14, p = 0.001) and RFS (HR 2.52, 95% CI 1.77–3.59, p = 0.001). NAR 3-year OS <8 was 95.3%, 8–16 was 88.6% and >16 was 80%. mrNAR related to OS (HR 2.96, 95% CI 1.38–6.34, p = 0.005) and RFS (HR 2.99, 95% CI 1.49–6.00, p = 0.002). 3-year OS for mrNAR <8 was 96.2%, 8–16 was 92.4% and >16 was 78%. On multivariate analysis, mrNAR was a stage-independent predictor of OS and RFS. mrNAR corresponded to NAR score category in only 15% (positive predictive value 0.23) and 47.5% (positive predictive value 0.48) of cases for categories <8 and >16, respectively.

Conclusions

Neoadjuvant rectal score is validated as a surrogate end-point for long-term outcomes. mrNAR categories do not correlate with NAR but have stage-independent prognostic value. mrNAR may represent a novel surrogate end-point for future neoadjuvant treatments that focus on organ preservation.     

Pathologic Response to Preoperative Therapy: Does It Mean What We Think It Means?

Tumors treated with preoperative chemotherapy or radiation often demonstrate evidence of response in the resection specimen. Pathologic response is often interpreted as a surrogate for recurrence or survival outcomes. With a valid surrogate for long-term outcomes, investigators can explore treatment strategies with immediate endpoints. The financial and time costs of trials measuring recurrence and survival may be lessened by using short-term pathologic outcomes as an endpoint. This review is intended to examine the current status of pathologic response as a surrogate for tumor behavior. We address questions regarding the definitions of pathologic response, as well as the current literature regarding the meaning of pathologic response for some common tumor types. We explore some of the potential confounding effects that may explain the frequent discordance between tumor response and patient outcomes. In addition, we address some alternative strategies to gauge the response of a tumor to preoperative therapy.     

Quality of life profile: from measurement to clinical application

Quality of life (QoL) can be assessed in an accurate, valid and reliable way by means of standardized QoL questionnaires and is an important endpoint in clinical trials today. The aim of this study is to implement quality of life as a diagnostic tool for problem-oriented follow-up care of cancer patients. This is done in the framework of an intervention study in the area of regional health care research using qualitative analysis and the methodological concept of barrier analysis. We developed the diagnostic tool by generating individual, graphic QoL profiles based on patients' responses to the EORTC QLQ-C30 and the corresponding disease-specific modules BR23 for breast cancer and CR38 for rectal cancer. The clinical application is investigated by assessing physicians' responses. The QoL profile is judged as a useful diagnostic tool by all participating physicians. It enables physicians to assess the QoL of the patient and incorporate the knowledge they gain in their daily practice. Especially in breast cancer follow-up care QoL profiles give added value to both patients and doctors. The next implementation steps have to extend the concept of QoL to larger groups of patients and physicians by overcoming the restraining factors as identified in the barrier analysis.     

Clinical trials,immunosuppression and renal transplantation: new trends in design and analysis

Clinical trials provide a framework to search for more effective and less toxic immunosuppressive agents to control renal transplant rejection. Some methodological aspects are presented. Patient selection and the choice of study endpoints are discussed with emphasis on standardized definitions and classification of histopathology, and on qualification and quantification of chronic rejection. Choosing a Bayesian or a frequentist approach and the afferent hypotheses is discussed together with the interpretation of a P-value and a confidence interval. Strategies for limiting the number of patients, increasing power and feasibility are reviewed, including discussion of surrogate endpoints. New approaches to statistical analysis are then presented, including intention-to-treat versus per-protocol analysis, analysis of correlated data, dependent censoring, and meta-analysis applied to renal transplantation. Pharmacoeconomics are finally introduced as necessary for implementation of decision making regarding therapeutic strategies. Reporting research increases its standards, and the CONSORT (Consolidated Standards of Reporting Trials) and QOROM (Quality of Reporting of Meta-analyses) criteria are to be integrated in the process of clinical trial procedures. In conclusion, observational studies are presented as part of an evidence-based approach in the hierarchy of evidence, keeping in mind that high quality, randomized, controlled trials are still necessary to decrease uncertainty in the field of renal transplantation.     

Challenges in the endocrine management of breast cancer

The goal of endocrine therapy in breast cancer is to block the action of estrogen on the tumor cells either by inhibiting estrogen from binding to the specific estrogen receptor or by inhibiting its synthesis. Tamoxifen, a selective estrogen receptor modulator, is the standard endocrine treatment for hormone receptor-positive breast cancer, both in the adjuvant and metastatic settings. Tamoxifen inhibits the binding of estrogen to the receptor, resulting in inhibition of hormone action. However, as tamoxifen is also weakly estrogenic, it may not be optimally effective and increases the risk of endometrial cancer and stroke. Furthermore, patients may be refractory or may become resistant to tamoxifen treatment. Since aromatase inhibitors (AI) block the synthesis of estrogen and have no intrinsic estrogenic activity, they have the potential to be more effective than tamoxifen. Their different mechanism of action and chemical structures may also circumvent tamoxifen resistance. Consequently, AIs are currently being evaluated as an alternative to tamoxifen treatment. A preclinical model has recently been developed to compare the efficacy of AIs and antiestrogens in different treatment schemes and to assist in the design of clinical trials. Current studies with the MCF-7Ca xenograft model are exploring the effects of combination and sequential therapy on tumor growth. The efficacy of AIs in the treatment of hormone receptor-positive breast cancer was first demonstrated in five multicenter second-line trials enrolling several hundreds of postmenopausal patients with metastatic breast cancer who had failed tamoxifen treatment. More recently, anastrozole demonstrated efficacy at least equivalent to that of tamoxifen in first-line randomized, phase III clinical trials in postmenopausal women with hormone receptor-positive or unknown metastatic breast cancer, whereas letrozole demonstrated superiority. The steroidal AI exemestane is currently under evaluation. Letrozole is the only AI to have been studied in a randomized, phase III trial in the neoadjuvant setting. In this trial, more patients underwent breast-conserving surgery with letrozole than with tamoxifen. Smaller phase II studies also suggest that both anastrozole and exemestane are active in the neoadjuvant setting. Because neoadjuvant trials permit temporal sampling of breast tissue, substudies in the phase III trial with letrozole have examined the impact of such biomarkers as estrogen receptor, progesterone receptor and epidermal growth factor receptor family members, HER-1 and HER-2, on patient response. AIs are currently under evaluation in the adjuvant setting, and preliminary results of the Arimidex, Tamoxifen Alone or in Combination (ATAC) trial have been reported. AIs have proven as safe as tamoxifen in trials in patients with metastatic breast cancer. Ongoing clinical trials in the adjuvant setting include companion studies of end-organ effects, particularly bone metabolism and lipid metabolism evaluations. Quality-of-life assessments are also parts of major clinical trials. A head-to-head quality-of-life assessment of anastrozole compared with letrozole demonstrated patient preference for letrozole. These assessments also clearly indicated the eagerness of patients to participate actively in treatment decisions     

多西他赛+卡铂联合曲妥珠单抗方案对早期人表皮生长因子受体2阳性乳腺癌的新辅助治疗效果

目的探讨多西他赛+卡铂联合曲妥珠单抗(TCH)方案对早期人表皮生长因子受体2(HER2)阳性乳腺癌的新辅助治疗效果。方法回顾性分析2013年1月至2018年12月北京大学第一医院乳腺疾病中心经治的522例早期HER2阳性乳腺癌患者的临床资料,占同期收治早期浸润性乳腺癌患者的21.80%(522/2 394)。其中113例接受TCH方案进行新辅助治疗,年龄[M(QR)]52(13)岁(范围:23~69岁)。记录TCH方案新辅助治疗后病理完全缓解(pCR,ypT0N0M0期)的例数,采用Miller-Payne标准进行病理学评价。采用Kaplan-Meier法计算无病生存率和总体生存率,采用Log-rank检验比较组间生存差异。结果接受曲妥珠单抗规范治疗患者(294例)的无病生存率优于未规范治疗患者(177例)(84.4%比72.4%,χ²=4.095,P=0.046)。发生3~4级不良反应的患者占全部患者的15.9%(18/113),包括3~4级中性粒细胞减少12例,腹泻6例。31例患者获得pCR(ypT0N0M0),pCR率为27.4%(31/113)。pCR患者与非pCR患者的无病生存率和总体生存率无差异(91.8%比85.0%,92.5%比90.5%,P值均>0.05)。病理学评价为G4~5的患者无病生存率优于G1~3患者(89.6%比81.5%,χ²=5.340,P=0.021),而总体生存率的差异无统计学意义(91.4%比89.1%,χ²=1.008,P=0.315)。结论早期HER2阳性乳腺癌采用TCH方案行新辅助治疗的效果较好,新辅助治疗后病理学评价为G4~5的患者的无病生存率更高。