Neoadjuvant Chemotherapy Is Associated with Improved Survival Compared with Adjuvant Chemotherapy in Patients with Triple-Negative Breast Cancer Only after Complete Pathologic Response

Introduction  

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer that is known to be chemosensitive. In patients with TNBC, we sought to compare survival outcomes between patients receiving neoadjuvant chemotherapy, with and without complete pathologic response (pCR), and those receiving adjuvant chemotherapy.     

Relationship Between Breast and Axillary Pathologic Complete Response in Women Receiving Neoadjuvant Chemotherapy for Breast Cancer

Annals of Surgical Oncology - We aim to delineate the relationship between breast and axillary pathologic complete response (pCR) in patients receiving neoadjuvant chemotherapy for breast cancer....     

Tumor Response Ratio Predicts Overall Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods.

Methods

Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I–III breast cancer who had NAC and pretreatment imaging at City of Hope (1997–2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0–0.4 (strong partial response, SPR), TRR > 0.4–1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan–Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders.

Results

There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016).

Conclusions

TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.     

A Nomogram to Predict the Pathologic Complete Response of Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer Based on Simple Laboratory Indicators

Annals of Surgical Oncology - Triple-negative breast cancer (TNBC) patients who achieve a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have better prognoses. This study...     

Neoadjuvant Chemotherapy of Breast Cancer: Tumor Markers as Predictors of Pathologic Response,Recurrence, and Survival

Abstract: This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR?) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR? patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR? patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant chemotherapy, but significantly better overall outcome. For both HR? and HR+, addition of NAT for HER2+ tumors results in both a superior response and outcome.     

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

PurposeIn breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study.Patients and MethodsBreast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS).ResultsOf 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85–1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88–1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history.ConclusionsIn this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.     

Correlation of Pathologic Complete Response with Survival After Neoadjuvant Chemotherapy in Bladder Cancer Treated with Cystectomy: A Meta-analysis

ContextNeoadjuvant chemotherapy before radical cystectomy (RC) is the preferred initial option for muscle-invasive bladder cancer (BCa). As in rectal and breast cancer, pathologic downstaging is associated with increased overall survival (OS).ObjectiveWe conducted a meta-analysis to determine whether pathologic complete response (pCR) (pT0N0M0) after neoadjuvant chemotherapy is associated with a better outcome in muscle-invasive BCa.Evidence acquisitionA systematic search was conducted in PubMed, Web of Science, Cochrane Collaboration's Central register of controlled trials, and Embase for publications reporting outcomes of patients with and without pCR. All patients underwent neoadjuvant cisplatin-based polychemotherapy and RC. The primary outcome reported as relative risk (RR) was OS. Secondary end points were recurrence-free survival (RFS) and cancer-specific survival other than distant and locoregional RFS. A meta-analysis was performed using the fixed effects model or random effects model. Overall heterogeneity for RFS and OS was assessed with forest plots and the Q test.Evidence synthesisA total of 13 trials were included, for a total of 886 patients analysed after neoadjuvant chemotherapy and RC, without any postoperative treatment. The pCR rate was 28.6%. Patients who achieved pCR in the primary tumour and the lymph nodes presented an RR for OS of 0.45 (95% confidence interval [CI], 0.36–0.56; p < 0.00001). The number needed to treat to prevent 1 death was 3.7 (absolute risk difference: −26%). The summary RR for RFS was 0.19 (95% CI, 0.09–0.39; p < 0.00001).ConclusionsPatients with BCa who achieved pCR (pT0N0M0 stage) after neoadjuvant chemotherapy have a better OS and RFS than do patients without pCR.     

Accuracy of the Combination of Mammography and Sonography in Predicting Tumor Response in Breast Cancer Patients After Neoadjuvant Chemotherapy

Background Residual tumor size after neoadjuvant chemotherapy is an important consideration in surgical planning. We examined the accuracy of the combination of mammography and sonography in predicting pathologic residual tumor size.Methods Tumor size was evaluated by physical examination, mammography, and sonography at diagnosis and before surgery in 162 breast cancer patients who received neoadjuvant chemotherapy. Agreement between the predicted and the pathologic responses and the predicted and the pathologic tumor sizes was calculated. The effect of invasive lobular carcinoma, high nuclear grade, hormone receptor positivity, and the presence of an extensive intraductal component on the accuracy of mammography and sonography in predicting pathologic residual tumor size was analyzed.Results Forty-two patients (25.9%) had a pathologic complete response (pCR). Overall agreement between predicted and pathologic responses was 53% for physical examination, 67% for mammography plus sonography, and 63% for physical examination plus mammography and sonography. The sensitivity of mammography and sonography in predicting pCR was 78.6%, and the specificity was 92.5%; the accuracy was 88.9%. Residual tumor size determined by mammography and sonography correlated with pathologic residual tumor size (r = .662); pathologic tumor size was within .5 cm of predicted in 69.1% of patients. Multivariate analysis showed that pathologic residual tumor size was underestimated for lobular carcinoma and overestimated for poorly differentiated tumors.Conclusions The combination of mammography and sonography has a high accuracy in predicting pCR after neoadjuvant chemotherapy. Agreement of residual tumor size in mammography and sonography with pathologic residual tumor size was moderate.Presented in part at the American Society of Breast Surgeons Seventh Annual Meeting, Baltimore, Maryland, April 5–9, 2006.     

Neoadjuvant Endocrine Therapy as an Alternative to Neoadjuvant Chemotherapy Among Hormone Receptor-Positive Breast Cancer Patients: Pathologic and Surgical Outcomes

Annals of Surgical Oncology - Neoadjuvant chemotherapy (NCT) is considered more effective in downstaging hormone receptor-positive (HR+) breast cancer than neoadjuvant endocrine therapy (NET),...     

Breast Cancer Subtypes can be a Predictor of Pathologic Complete Response and Survival in the Neoadjuvant Setting for T4 Noninflammatory Breast Cancer

Background: The aim of this study is to identify whether the breast cancer subtypes are predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and survival in patients with T4 noninflammatory breast cancer.

Methods: The records of 181 patients treated with anthracycline ± taxane based NAC followed by mastectomy and radiation therapy ± hormonotherapy were evaluated. The role of intrinsic subtypes of the tumor including luminal A, luminal B, HER2, and triple-negative on pCR and survival were analyzed.

Results: The median follow-up was 44 months (range:16–82 months). All patients received a median four cycles of NAC. Twenty-three patients (12.7%) were found to have pCR. In the univariate analysis, the intrinsic subtypes of the tumor had significant effect on pCR (p < 0.01). Also, intrinsic subtypes were significant predictors of pCR to NAC in the multivariate analysis (p < 0.01; hazard ratio, 2.4; 95% confidence interval, 1.1–6.8). While patients with triple-negative tumors had the highest rate of pCR (29%), this rate was the lowest in patients with HER2 tumors (4.2%). Five-year DFS was also significantly lower in patients with triple-negative (24%) and HER2 (21%) tumors compared to luminal A (61%) subtype (p < 0.0001). Likewise, 5-year OS was poorer in patients with triple-negative tumors (30%) and HER2 tumors (%31) compared to both luminal A (70%) and luminal B (68%) subtypes (p < 0.0001).

Conclusions: It can be concluded that breast cancer subtyping defines the extent of response to NAC and has a significant effect on survival in patients with T4 noninflammatory breast cancer.     

Breast-Conserving Surgery After Tumor Downstaging by Neoadjuvant Chemotherapy is Oncologically Safe for Stage III Breast Cancer Patients

Background

We conducted a retrospective study to evaluate the local recurrence (LR) rate depending on the use of neoadjuvant chemotherapy (NCT) and to determine the oncologic safety of breast-conserving surgery (BCS) after NCT by comparing LR between patients treated with BCS and mastectomy in clinical stage III breast cancer patients.

Patients and Methods

Between 2004 and 2007, 166 patients underwent BCS or mastectomy after NCT (NCT group) and 193 patients underwent surgery first (surgery group) in clinical stage III breast cancer patients. Patients whose tumor size became ≤4 cm after NCT, 57 patients underwent mastectomy (mastectomy group) 39 patients underwent preplanned BCS (preplanned BCS group), and 33 patients underwent downstaged BCS (downstaged BCS group). The recurrence rates between the groups and risk factors for LR were analyzed.

Results

The 5-year LR-free survival rates were 93.6 % in the NCT group and 95.9 % in the surgery group (P = 0.108). In the NCT group, the 5-year LR-free survival rates were 96.3 % in the mastectomy group, 94.7 % in the preplanned BCS group and 90.9 % in the downstaged BCS group (P = 0.669). High expression of Ki-67 was a predictor of LR in patients in three groups (Hazard ratio 8.300, P = 0.049).

Conclusions

Our findings suggest that BCS after NCT in clinical stage III patients is oncologically safe in terms of LR if breast tumor size is ≤4 cm after NCT and Ki-67 is a predictor of LR after NCT.     

ASO Visual Abstract: Prediction of Pathologic Complete Response in Breast Cancer Patients Comparing Magnetic Resonance Imaging with Ultrasound in the Neoadjuvant Setting

Annals of Surgical Oncology -     

Pathologic Predictors of Tumor Response to Preoperative Chemotherapy in Locally Advanced Breast Carcinoma

Abstract: Tumor response to preoperative chemotherapy varies from complete to partial to none. To evaluate pathologic predictors of tumor response to preoperative chemotherapy, we reviewed 287 cases of locally advanced breast carcinoma treated with chemotherapy prior to definitive surgery. The patients ranged in age from 18 to 79 years (mean, 48 years). There were 77 (26.8%) patients with stage II disease, 194 (67.6%) with stage III disease, and 16 (5.6%) with stage IV disease. Following the initial diagnosis of invasive carcinoma (by fine-needle aspirate or cutting needle biopsy), the patients received three to four cycles of both doxorubicin-based and cyclophosphamide-based regimens followed by mastectomy or lumpectomy with axillary dissection. The pathologic parameters that were evaluated included stage, clinical tumor size, and tumor nuclear grade (NG). The latter was performed on fine-needle aspirates using Black's nuclear grading system wherein NG1 was considered well differentiated; NG2, moderately differentiated; and NG3, poorly differentiated. Based on pathologic examination of the resected specimens, tumor responses were categorized into complete response, partial response, no response, or progressive disease. The overall response rate was 71% (12% complete and 59% partial responses). In univariate analyses, tumor size and nuclear grade were significantly related to pathologic tumor response to chemotherapy (p = 0.04 and p = 0.0003, respectively), while disease stage was not (p = 0.17). In multivariate analyses, size remained significant even when NG was present in the equation (p = 0.013). Similarly, when size was included, NG remained significant (p = 0.002). NG3 tumors showed better response than NG2 or NG1 tumors did. While 19.3% of NG3 tumors showed complete response, none of the NG1 tumors completely responded to chemotherapy. Initial tumor size was inversely proportional to degree of tumor response. Our findings indicate that tumor clinical size and nuclear grade are important independent predictors of response to preoperative chemotherapy and that poorly differentiated tumors and small tumors showed the most response.     

Clinical Usefulness of AJCC Response Criteria for Neoadjuvant Chemotherapy in Breast Cancer

Purpose

Recently, the American Joint Committee on Cancer (AJCC) 7th edition proposed new response criteria for neoadjuvant chemotherapy (NAC) in breast cancer. The purpose of this study was to evaluate the clinical usefulness of AJCC response criteria.

Methods

A total of 398 consecutive stage II or III breast cancer patients who received NAC were enrolled in this study. AJCC response criteria were as follows: (1) complete response (CR)—absence of invasive carcinoma in the breast and node; (2) partial response (PR)—decrease in either or both T or N stage; (3) no response (NR)—no change or increase in either or both T or N stage.

Results

Complete response, PR, and NR by AJCC criteria were 9.8, 59.3, and 30.7 %, respectively. Among the 398 patients, 337 patients were available for both paired pre- and post- breast MRI and chest CT. AJCC response criteria were significantly associated with RECIST criteria (P < 0.001). AJCC response was significantly associated with relapse-free survival (RFS) and overall survival (OS). The 5-year RFS rates were 89.6 % in CR, 74.1 % in PR, and 62.6 % in NR (P = 0.002). The 5-year OS rates were 97.4 % in CR, 88.6 % in PR, and 78.3 % in NR (P = 0.012). When adjusting potential prognostic factors, AJCC response was independently associated with RFS and OS.

Conclusions

AJCC response criteria for NAC in breast cancer have clinical usefulness in evaluating response of NAC, as well as predicting survival. AJCC response criteria can discriminate among patient subgroups with respect to survival.     

MRI Phenotype Is Associated With Response to Doxorubicin and Cyclophosphamide Neoadjuvant Chemotherapy in Stage III Breast Cancer

Background: The preferred management for women with stage II or locally advanced breast cancer (LABC) is neoadjuvant chemotherapy. Pathologic response to chemotherapy has been shown to be an excellent predictor of outcome. Surrogates that can predict pathologic response and outcome will fuel future changes in management. Magnetic resonance imaging (MRI) demonstrates that patients with LABC have distinct tumor patterns. We investigated whether or not these patterns predict response to therapy.Methods: Thirty-three women who received neoadjuvant doxorubicin and cyclophosphamide chemotherapy for 4 cycles and serial breast MRI scans before and after therapy were evaluated for this study. Response to therapy was measured by change in the longest diameter on the MRI.Results: Five distinct imaging patterns were identified: circumscribed mass, nodular tissue infiltration diffuse tissue infiltration, patchy enhancement, and septal spread. The likelihood of a partial or complete response as measured by change in longest diameter was 77%, 37.5%, 20%, and 25%, respectively.Conclusions: MRI affords three-dimensional characterization of tumors and has revealed distinct patterns of tumor presentation that predict response. A multisite trial is being planned to combine imaging and genetic information in an effort to better understand and predict response and, ultimately, to tailor therapy and direct the use of novel agents.     

乳腺癌新辅助化疗后局部区域外科处理进展

目的探讨乳腺癌新辅助化疗后对局部区域的外科处理策略。方法对近年来有关乳腺癌新辅助化疗降期后保乳治疗、同侧乳房复发的相关因素、原发肿瘤病理退缩模式以及前哨淋巴结活检等局部区域的外科处理的相关文献进行综述。结果①新辅助化疗可使乳腺原发肿瘤降期,提高保乳手术的比率,但通过新辅助化疗降期后保乳手术患者可能存在较高的同侧乳腺肿瘤复发风险。目前比较趋于一致的影响新辅助化疗降期后保乳治疗的同侧乳腺肿瘤复发率的相关因素为残余肿瘤呈多中心模式、残余肿瘤直径〉2cm。新辅助化疗后原发肿瘤病理退缩模式及相关因素尚不明确。②新辅助化疗前、后前哨淋巴结活检（SLNB）均是可行的并获得指南与专家共识的认可,初始腋窝淋巴结阴性患者更能从新辅助化疗后SLNB中获益,初始腋窝淋巴结阳性患者新辅助化疗转阴性后行SLNB替代ALND的前景可期,但需要获得临床认可的成功率和假阴性率及与ALND相似的局部区域复发率及总生存率。结论无论乳腺癌新辅助化疗的临床和影像学疗效如何,外科处理仍然是目前降低局部区域复发风险的重要治疗手段。分子分型时代,我们可以依据乳腺癌初始分期及新辅助化疗的疗效对乳腺癌患者施行个体化的局部区域外科处理