Hormone receptor status and pathologic response of HER2-positive breast cancer treated with neoadjuvant chemotherapy and trastuzumab

Background: The aim of this study was to compare the extent of pathologic response in patients with HER2-positive (HER2+) breast cancer treated with standard neoadjuvant chemotherapy, with or without trastuzumab (H), according to hormone receptor (HR) status.Patients and methods: We included 199 patients with HER2+ breast cancer from three successive cohorts of neo-adjuvant chemotherapy on the basis of paclitaxel (Taxol) (P) administered weekly (w) or three weekly (3-w), followed by 5-fluorouracil (F), doxorubicin (A) or epirubicin (E), and cyclophosphamide (C). Residual cancer burden (RCB) was determined from pathologic review of the primary tumor and lymph nodes and was classified as pathologic complete response (pCR) or minimal (RCB-I), moderate (RCB-II), or extensive (RCB-III) residual disease.Results: In HR-positive (HR+) cancers, a higher rate of pathologic response (pCR/RCB-I) was observed with concurrent H + 3-wP/FEC (73%) than with 3-wP/FEC (34%, P = 0.002) or wP/FAC (47%; P = 0.02) chemotherapy alone. In HR-negative (HR-) cancers, there were no significant differences in the rate of pathologic response (pCR/RCB-I) from 3-wP/FAC (50%), wP/FAC (68%), or concurrent H + 3-wP/FEC (72%).Conclusions: Patients with HR+/HER2+ breast cancer obtained significant benefit from addition of trastuzumab to P/FEC chemotherapy; pathologic response rate was similar to that seen in HR-/HER2+ breast cancers.     

Dual HER2-blockade with pertuzumab and trastuzumab in HER2-positive early breast cancer: a subanalysis of data from the randomized phase III GeparSepto trial

BackgroundThe neoadjuvant phase III GeparSepto study showed that substituting nab-paclitaxel for standard solvent-based paclitaxel significantly improved the pathologic complete response (pCR) rate achieved with a sequential neoadjuvant chemotherapy regimen of paclitaxel, epirubicin, and cyclophosphamide for high-risk primary breast cancer. Recent trials demonstrated that in HER2+ breast cancer pCR can be increased by using pertuzumab in addition to trastuzumab and chemotherapy. The present analysis focuses on efficacy and safety data from the subset of patients with HER2+ tumors from the GeparSepto trial (n = 396) in comparison to the HER2- cohort.Patients and methodsPatients with histologically confirmed breast cancer (n = 1206) received four cycles of weekly paclitaxel [either solvent-based (Pac) or nab-paclitaxel (nab-Pac), according to randomization] followed by 4 cycles of epirubicin 90 mg/m² plus cyclophosphamide 600 mg/m² q3w, with concurrent trastuzumab and pertuzumab q3w for those with HER2+ tumors. The primary endpoint was pCR defined as ypT0 ypN0.ResultsHigher rates of pCR were achieved in HER2+ than in HER2- tumors (57.8% versus 22.0%,P < 0.0001), with the highest rate in the HER2+/HR- cohort (71.0%; 66.7% Pac, 74.6% nab-Pac). In HER2+/HR+ tumors, the pCR rate was 52.9% (49.7% Pac, 56.4% nab-Pac). Grade ≥3 toxic effects were significantly more common in HER2+ than in HER2- patients, with grade 3–4 diarrhea in 7.6% versus 0.9% (P < 0.001) and febrile neutropenia in 6.3% versus 3.3% (P = 0.023) of patients. Left ventricular ejection fraction decreases from baseline were uncommon, with 2.0% versus 0.4% of patients showing decreases to <50% along with a ≥10% decrease from baseline.ConclusionIn HER2+ early breast cancer, a dual HER2-targeted combination of pertuzumab and trastuzumab, together with taxane–epirubicin–cyclophosphamide neoadjuvant chemotherapy, achieved high rates of pCR.     

A Phase II Neoadjuvant Trial of Sequential Nanoparticle Albumin-Bound Paclitaxel Followed by 5-Fluorouracil/Epirubicin/Cyclophosphamide in Locally Advanced Breast Cancer

BackgroundNeoadjuvant chemotherapy has become standard treatment for women with locally advanced breast cancer (LABC). Various regimens have explored the addition of newer agents to determine safety and efficacy. The aim of this phase II study was to incorporate albumin-bound paclitaxel with sequential anthracycline-based therapy.Patients and MethodsSixty-six women with LABC but without prior treatment and regardless of hormone receptor or HER2 status were enrolled. All patients were to receive albumin-bound paclitaxel weekly for 12 weeks followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Trastuzumab was allowed in HER2-positive (HER2⁺) patients. Primary endpoint was pathologic complete response (pCR; CR) in breast. Secondary endpoints included pCR in breast and nodes, clinical CR, 2-year progression-free survival, and overall survival.ResultsSixty-five patients received at least 1 dose of chemotherapy and were included in this analysis. Sixty-three patients completed 4 cycles of albumin-bound paclitaxel. Sixty-two patients received at least 1 dose of FEC, and 58 completed 4 cycles. Seventeen of 19 HER2⁺ women received trastuzumab. The pCR in breast was 29% (19 of 65). For the HER2⁺ subset, the pCR was 58% (11 of 19). Both albumin-bound paclitaxel and FEC were well tolerated. The most significant toxicities were grade 2/3 neuropathy (16%) with albumin-bound paclitaxel and grade 3/4 febrile neutropenia (7%) with FEC.ConclusionAlbumin-bound paclitaxel given over 12 weeks is well tolerated. Albumin-bound paclitaxel should be further evaluated in a randomized setting in both adjuvant and neoadjuvant trials.     

HER2 and response to anthracycline-based neoadjuvant chemotherapy in breast cancer

BackgroundThe predictive role of human epidermal growth factor receptor 2 (HER2) to adjuvant anthracycline-based chemotherapy remains controversial. Here, we investigated the association between HER2 status and pathological response in breast cancer patients who received neoadjuvant anthracycline-based regimens.Patients and methodsWomen (n = 538) with operable primary breast cancer received neoadjuvant anthracycline-based chemotherapy. Pathological complete response (pCR) was defined as no invasive breast tumor cells in breast after completion of neoadjuvant chemotherapy. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core biopsy breast cancer tissue obtained before initiation of neoadjuvant chemotherapy.ResultsIn this cohort of 538 patients, 23.9% of patients achieved a pCR in their breast. HER2-positive tumors had a lower rate of pCR than did HER2-negative tumors (14.7% versus 25.7%, P = 0.013); negative HER2 status remained as an independent favorable predictor of pCR after adjusted for age, estrogen receptor, progesterone receptor, tumor size, chemotherapy cycles, and tumor grade in a multivariate analysis (odds ratio = 3.14; 95% confidence interval = 1.60–6.16, P = 0.001). Furthermore, patients with a pCR had a higher 3-year disease-free survival (DFS) rate than did patients without a pCR (P = 0.007).ConclusionWomen with HER2-negative breast cancers rather than HER2-positive tumors benefit from anthracycline-based neoadjuvant chemotherapy.     

The Role of Immunohistochemistry in Breast Cancer Patients Treated With Neoadjuvant Chemotherapy: An Old Tool With an Enduring Prognostic Value

BackgroundTo assess the molecular subtypes determined by hormonal receptors (HR) and human epidermal growth factor receptor 2 (HER2) status and the role of proliferation measured by the Ki-67 marker as predictive and prognostic factors in breast cancer patients treated with neoadjuvant chemotherapy.MethodsA total of 127 breast cancer patients were treated with neoadjuvant chemotherapy every 2 weeks as part of 2 studies. Study A consisted of the administration of Adriamycin (40 mg/m²) on day 1 plus paclitaxel (150 mg/m²) and gemcitabine 2000 mg/m²) on day 2 for 6 cycles (n = 54). Study B consisted of the administration of epirubicin (90 mg/m²), cyclophosphamide (600 mg/m²) on day 1 for 3 cycles, followed by the administration of paclitaxel (150 mg/m²) and gemcitabine 2500 (mg/m²) on day 1 with or without trastuzumab according to HER2 status (n = 73). In study A, patients did not receive trastuzumab regardless of HER2 status. The molecular subtypes of the patients with breast cancer were classified as 49% HR⁺/HER2^?, 17.5% HR⁺/HER2⁺, 13.5% HR^?/HER2⁺, and 20% HR^?/HER2^?.ResultsPathologic complete response (pCR), defined as the absence of invasive cells in the breast and the lymph nodes, was achieved in 35 (28%) patients. The pCR rate was significantly different between the molecular subtypes of breast cancer, with 9% in HR⁺/HER2^?, 23% in HR⁺/HER2⁺, 50% in HR^?/HER2⁺, and 56% in HR^?/HER2^? tumors (P < .001). The pCR rate was significantly higher in tumors that had high Ki-67 (≥20%) expression and were HR^?. HER2⁺ was associated with a higher trend of pCR but did not reach statistical significance. The median follow-up was 81 months (r = 15-150 months). Patients who achieved a pCR had a significantly lower recurrence (P = .01) and higher overall survival (P = .02) compared with those who did not achieve pCR. A multivariate analysis revealed that pCR (hazard ratio 0.24 [95% CI, 0.07-0.7]; P = .019), the molecular subtype (hazard ratio 0.3 [95% CI, 0.1-0.8]; P = .02), and the Ki-67 index (hazard ratio 3.2 [95% CI, 1.4-7.1]; P = .004) were significant independent predictors of disease-free survival. Similar results were obtained for overall survival, in which the pCR rate (hazard ratio 0.119 [95% CI, 0.028-0.5]; P = .004), the molecular subtype (hazard ratio 0.17 [95% CI, 0.03-0.86]; P = .02), and the Ki-67 index (hazard ratio 3.6 [95% CI, 1.3-9.7]; P = .01) also displayed a significant influence on survival.ConclusionsMolecular subtypes and Ki-67 index were independent prognostic factors for disease-free survival and overall survival in breast cancer patients treated with neoadjuvant chemotherapy. A high rate of Ki-67 and HR^? expression were predictors of pCR.     

A Phase II Trial of a Neoadjuvant Platinum Regimen for Locally Advanced Breast Cancer: Pathologic Response,Long-Term Follow-up,and Correlation With Biomarkers

PurposeThe purpose of this study is to determine the response, tolerability, and long-term outcome of a neoadjuvant platinum-containing regimen for locally advanced breast cancer (LABC) and to search for a correlation between pathologic complete response (pCR) and predefined biomarkers in this cohort.Patients and MethodsPatients with LABC received 8 cycles of either sequence A or B. Sequence A was doxorubicin 60 mg/m² and paclitaxel 175 mg/m² (AT) every 3 weeks × 4 followed by cisplatin (C) 60 mg/m² and paclitaxel 90 mg/m² (CT) every 2 weeks × 4. Sequence B was CT × 4 (with paclitaxel dose escalation) followed by AT × 4. In addition to estrogen receptor (ER) and HER2, immunohistochemistry for MDR-1, MRP-1, topoisomerase IIα (topo IIα), and p53 was performed.ResultsA total of 88 patients were evaluable for response and toxicity. Median follow-up was 97 months. The overall pCR rate was 21.5%. For subgroups ER+/HER2+, HER2+ and double negative (ER+/HER2+) disease, the pCR rates were 5.9%, 23.3%, and 35%, respectively (P = .006). Five-year overall survival for the entire cohort was 71.1%. Five-year overall survival was 88.1% (95% CI, 77.1%-99.1%) for the ER+/HER2+ group compared with 68.5% (95% CI, 51.3%-85.7%) and 49.5% (95% CI, 27.4%-71.6%) in the HER2+ and “double-negative” group, respectively (P = .0077). Overexpression of topo IIα was correlated with pCR (P < .001). There were no toxic deaths.ConclusionA platinum-containing neoadjuvant regimen was well tolerated and achieved a pCR comparable to other recent studies of multiagent chemotherapy. Further studies tailored for specific breast cancer subtypes are required.     

Association between HER2 status and response to neoadjuvant anthracycline followed by paclitaxel plus carboplatin chemotherapy without trastuzumab in breast cancer

Background

We recently showed HER2-positive breast cancers are less likely to respond to neoadjuvant anthracycline chemotherapy. Here, we investigated whether HER2-positive breast cancers responded to sequential neoadjuvant anthracycline followed by paclitaxel plus carboplatin regimen in the absence of trastuzumab.

Methods

Women (n=372) with operable primary breast cancer initially received two cycles of neoadjuvant anthracyclines, the clinical tumor response was assessed, then patients were received four cycles of paclitaxel plus carboplatin regimen. All the patients did not received trastuzumab treatment in the neoadjuvant setting. HER2 status was determined by immunohistochemistry and/or by fluorescence in situ hybridization in core-biopsy breast cancer tissue obtained before the neoadjuvant chemotherapy.

Results

Eighteen percent (67/372) of patients achieved a pathologic complete response (pCR) in their breast. HER2-positive tumors had a significant higher pCR rate than HER2-negative tumors (33.0% versus 13.5%, P<0.001) in this cohort of 372 patients, and positive HER2 status remained an independent favorable predictor of pCR in a multivariate analysis [odds ratio (OR), 2.26; 95% confidence interval (CI), 1.18 to 4.36, P=0.015]. Furthermore, patients who responded to initial anthracycline regimens were more likely to respond to paclitaxel plus carboplatin than patients who did not (pCR, 27.2% versus 14.6%, P=0.005). Patients with HER2-positive tumors exhibited a significant higher pCR rate than did patients with HER2-negative tumors in both anthracycline response group (40.5% versus 20.0%, P=0.025) and anthracycline non-response group (28.3% versus 11.3%, P=0.002).

Conclusions

Under the circumstance of no trastuzumab treatment, women with HER2-positive cancers derive a large benefit from paclitaxel-carboplatin-based neoadjuvant chemotherapy.     

原发性乳腺癌分子分型与新辅助化疗疗效及预后的相关性

目的 探讨原发性乳腺癌分子分型与新辅助化疗疗效及预后之间的相关性。方法 回顾性分析河南省肿瘤医院收治的204例接受新辅助化疗患者的临床病理资料,分为Luminal A、LuminalB、HER2阳性和三阴乳腺癌4种亚型,分析乳腺癌分子分型对新辅助化疗疗效及预后的预测作用。结果 204例患者中,40例（19.6％）为Luminal A亚型,46例（22.5％）为Luminal B亚型,36例（17.6％）为HER2阳性亚型,82例（40.2％）为三阴乳腺癌亚型。HER2阳性（22.2%）及三阴乳腺癌亚型（22.4%）的病理完全缓解（pCR）率明显高于Luminal A亚型（2.5％）及Luminal B亚型（6.5％）,差异有统计学意义（P=0.03）。与Luminal亚型相比,HER2阳性及三阴乳腺癌亚型具有更差的无病生存期（DFS）（P=0.001）和OS（P=0.002）;剔除获得pCR的患者,单独评价存在肿瘤残留的患者,我们发现HER2阳性及三阴乳腺癌亚型比Luminal亚型具有更差的DFS（P<0.001）和OS（P<0.001）。获得pCR的乳腺癌患者的5年DFS和总生存期（OS）均明显高于化疗后仍有癌残留的患者（P=0.002, P=0.012）。结论 相对于Luminal亚型,HER2 阳性和三阴乳腺癌亚型对新辅助化疗更为敏感,更易达到pCR;但是HER2阳性和三阴乳腺癌亚型预后反而更差。     

A gene expression signature of Retinoblastoma loss-of-function predicts resistance to neoadjuvant chemotherapy in ER-positive/HER2-positive breast cancer patients

Purpose

HER2-positive (HER2+) breast cancers show heterogeneous response to chemotherapy, with the ER-positive (ER+) subgroup deriving less benefit. Loss of retinoblastoma tumor suppressor gene (RB1) function has been suggested as a cardinal feature of breast cancers that are more sensitive to chemotherapy and conversely resistant to CDK4/6 inhibitors. We performed a retrospective analysis exploring RBsig, a gene signature of RB loss, as a potential predictive marker of response to neoadjuvant chemotherapy in ER+/HER2+ breast cancer patients.

Methods

We selected clinical trials of neoadjuvant chemotherapy?±?anti-HER2 therapy in HER2+ breast cancer patients with available information on gene expression data, hormone receptor status, and pathological complete response (pCR) rates. RBsig expression was computed in silico and correlated with pCR.

Results

Ten studies fulfilled the inclusion criteria and were included in the analysis (514 patients). Overall, of 211 ER+/HER2+ breast cancer patients, 49 achieved pCR (23%). The pCR rate following chemotherapy?±?anti-HER2 drugs in patients with RBsig low expression was significantly lower compared to patients with RBsig high expression (16% vs. 30%, respectively; Fisher’s exact test p?=?0.015). The area under the ROC curve (AUC) was 0.62 (p?=?0.005). In the 303 ER-negative (ER?)/HER2+ patients treated with chemotherapy?±?anti-HER2 drugs, the pCR rate was 43%. No correlation was found between RBsig expression and pCR rate in this group.

Conclusions

Low expression of RBsig identifies a subset of ER+/HER2+ patients with low pCR rates following neoadjuvant chemotherapy?±?anti-HER2 therapy. These patients may potentially be spared chemotherapy in favor of anti-HER2, endocrine therapy, and CDK 4/6 inhibitor combinations.

     

Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21 755 patients from the Japanese breast cancer registry

BackgroundWe investigate rates of pathologic complete response (pCR) and tumor expression of ER, PgR, HER2 discordance after neoadjuvant chemotherapy using Japanese breast cancer registry data.Patients and methodsRecords of more than 300 000 breast cancer cases treated at 800 hospitals from 2004 to 2013 were retrieved from the breast cancer registry. After data cleanup, we included 21 755 patients who received neoadjuvant chemotherapy and had no distant metastases. pCR was defined as no invasive tumor in the breast detected during surgery after neoadjuvant chemotherapy. HER2 overexpression was determined immunohistochemically and/or using fluorescence in situ hybridization.ResultspCR was achieved in 5.7% of luminal tumors (n = 8730), 24.6% of HER2-positive tumors (n = 4403), and 18.9% of triple-negative tumors (n = 3660). Among HER2-positive tumors, pCR was achieved in 31.6% of ER-negative tumors (n = 2252), 17.0% of ER-positive ones (n = 2132), 31.4% of patients who received trastuzumab as neoadjuvant chemotherapy (n = 2437), and 16.2% of patients who did not receive trastuzumab (n = 1966). Of the 2811 patients who were HER2-positive before treatment, 601 (21.4%) had HER2-negative tumors after neoadjuvant chemotherapy, whereas 340 (3.4%) of the 9947 patients with HER2-negative tumors before treatment had HER2-positive tumors afterward. Of the 10 973 patients with ER-positive tumors before treatment, 499 (4.6%) had ER-negative tumors after neoadjuvant chemotherapy, whereas 519 (9.3%) of the 5607 patients who were ER-negative before treatment had ER-positive tumors afterward.ConclusionWe confirmed that loss of HER2-positive status can occur after neoadjuvant treatment in patients with primary HER2-positive breast cancer. We also confirmed that in practice, differences in pCR rates between breast cancer subtypes are the same as in clinical trials. Our data strongly support the need for retest ER, PgR, HER2 of surgical sample after neoadjuvant therapy in order to accurately determine appropriate use of targeted therapy.     

Incident comorbidities and all-cause mortality among 5-year survivors of Stage I and II breast cancer diagnosed at age 65 or older: a prospective-matched cohort study

Addition of carboplatin to neoadjuvant chemotherapy in HER2-negative breast cancer may improve pathological complete response (pCR) rates. We evaluated the efficacy and safety of carboplatin and weekly paclitaxel (wPTX) followed by cyclophosphamide, epirubicin, and 5-fluorouracil (CEF) as neoadjuvant chemotherapy for HER2-negative breast cancer. Patients with stage II/IIIA HER2-negative breast cancer were randomly assigned to preoperatively receive CP-CEF (four 3-week cycles of carboplatin [area under the curve 5 mg/mL/min, day 1] and wPTX [80 mg/m², day 1, 8, 15] followed by four 3-week cycles of CEF [500/100/500 mg/m²] or P-CEF (four cycles of wPTX followed by four cycles of CEF). The primary objective was pCR rate. Of 181 eligible patients, 89 were randomly assigned to the CP-CEF and 92 to the P-CEF. Two patients in each arm refused to receive neoadjuvant chemotherapy. Overall 88 patients in the CP-CEF and 91 patients in the P-CEF were assessable for efficacy and safety. The pCR rate in the CP-CEF was significantly higher than that in the P-CEF (31.8 vs. 17.6 %, one-sided P = 0.01). Among patients with triple-negative breast cancer, the pCR rate in the CP-CEF was significantly higher than that in the P-CEF [61.2 (23/37) vs. 26.3 % (10/38), P = 0.003]. Grade 3–4 neutropenia was observed in the CP-CEF more frequently than in the P-CEF (65.9 vs. 38.5 %). Adding carboplatin to neoadjuvant wPTX followed by CEF for HER2-negative breast cancer improved the pCR rate and exacerbated hematotoxicity.     

Tumour molecular subtyping according to hormone receptors and HER2 status defines different pathological complete response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

Purpose  To study the role of breast cancer molecular subtypes according to hormone receptors and HER2 status as a predictive factor for pathological complete response (pCR) to neoadjuvant chemotherapy. Patients and methods  Eligible patients received one of the two chemotherapy schedules every two weeks with prophylactic growth factor support; schedule A: epirubicin 90 mg/m²-cyclophosphamide 600 mg/m² d1 for 3 cycles followed by a second sequence with paclitaxel (P) 150 mg/m²-gemcitabine (G) 2500 mg/m² d1±trastuzumab (T) 2 mg/kg/week according to HER2 status (n=73); schedule B: adriamycin (40 mg/m²) d1 plus P (150 mg/m²)-G (2000 mg/m²) d2 for 6 cycles (n=54). Subsequently, patients underwent surgery, radiotherapy and/or adjuvant hormonal therapy according to standard practice. Results  A total of 127 patients were evaluated. Forty-three patients (33.9%) achieved a pCR (50% in patients with HER2+tumours treated with T). Patients treated with chemotherapy alone (n=107, 18 HER2+) had a pCR of 32% (p=0.068). The pCR rate for patients with triple negative (HR and HER2−) cancers was 58.3%, 39.5% for HER2+ and 5.4% for ER/PR+ and HER2− (p<0.001). No differences in disease-free survival (DFS) were noted as a function of pCR, HER2 and HR status or treatment received (±T). However, statistical differences in DFS were observed as a function of whether patients had + or − axillar lymph nodes. Patients with + lymph node disease did worse (3 years DFS of 53.7% vs. 81.5%, p=0.025). Breastconserving surgery was performed in 77 patients (60.6%). Conclusion  Tumour molecular subtyping defines different pCR to neoadjuvant chemotherapy (NC) but has no impact over DFS in patients with LABC. Although no significant correlation between HER2 status and trastuzumab therapy with pCR was found, probably due to the small number of patients, a favourable trend was observed in the group of HER2+ tumours treated with T.     

Association between Pathological Complete Response and Outcome Following Neoadjuvant Chemotherapy in Locally Advanced Breast Cancer Patients

Purpose

We aimed to determine the rate of pathological complete response (pCR), clinicopathological factors associated with pCR, and clinical outcomes following neoadjuvant chemotherapy in locally advanced breast cancer.

Methods

Medical records of patients who had undergone neoadjuvant chemotherapy for breast cancer between January 2007 and September 2011 were retrospectively reviewed, and the pCR rates were calculated according to three sets of criteria: the National Surgical Adjuvant Breast and Bowel Project (NSABP), the MD Anderson Cancer Center (MDACC), and the German Breast Group (GBG). Tumors were classified as luminal A like, luminal B like, human epidermal growth factor receptor 2 (HER2), or triple-negative. pCR and clinical outcome, including overall survival (OS) and disease-free survival (DFS) rates were analyzed at the median follow-up of 54.2 months.

Results

Of a total of 179 patients who had received neoadjuvant chemotherapy, 167 patients (93.3%) had locally advanced breast cancer and 12 patients (6.7%) had early-stage breast cancer. The majority of patients (152 patients, 89.4%) received anthracycline-based neoadjuvant chemotherapy. The objective clinical response rate was 61.5%, comprising clinical partial response in 5.5% and clinical complete response in 3.9% of patients. Twenty-one (11.7%), 20 (11.2%), and 17 patients (9.5%) achieved pCR according to NSABP, MDACC, and GBG definitions, respectively. pCR rates, as defined by NSABP, according to breast cancer subtype were 4.4%, 9.7%, 24.2%, and 19.2% in luminal A like, luminal B like, HER2, and triple-negative subtypes, respectively. Patients who achieved pCR had significantly better DFS (5-year DFS rates, 80% vs. 53%, p=0.030) and OS (5-year OS rates, 86% vs. 54%, p=0.042) than those who did not.

Conclusion

The pCR rate following neoadjuvant chemotherapy for breast cancer in Thai women attending our institution was 11.7%; pCR was more frequently observed in HER2 and triple-negative breast tumor subtypes. Patients who achieved pCR had significantly improved survival.     

A Phase II Study Evaluating the Safety and Efficacy of Sunitinib Malate in Combination With Weekly Paclitaxel Followed by Doxorubicin and Daily Oral Cyclophosphamide Plus G-CSF as Neoadjuvant Chemotherapy for Locally Advanced or Inflammatory Breast Cancer

IntroductionNeoadjuvant chemotherapy is standard treatment for locally advanced breast cancer (LABC) or inflammatory breast cancer (IBC). We hypothesized that adding sunitinib, a tyrosine kinase inhibitor with antitumor and antiangiogenic activity, to an anthracycline and taxane regimen would improve pathologic complete response (pCR) rates to a prespecified endpoint of 45% in patients with HER2-negative LABC or IBC.MethodsWe conducted a multicenter, phase II trial of neoadjuvant sunitinib with paclitaxel (S+T) followed by doxorubicin and cyclophosphamide plus G-CSF for patients with HER2-negative LABC or IBC. Patients received sunitinib 25 mg PO daily with paclitaxel 80 mg/m² IV weekly ×12 followed by doxorubicin 24 mg/m² IV weekly + cyclophosphamide 60 mg/m² PO daily with G-CSF support. Response was evaluated using pCR in the breast and the CPS + EG score (clinical-pathologic scoring + estrogen receptor [ER] and grade).ResultsSeventy patients enrolled, and 66 were evaluable for efficacy. Eighteen patients (27%) had pCR in the breast (10 had ER⁺ disease and 8 had triple-negative disease). When defining response as pCR and/or CPS + EG score ≤2, 31 (47%) were responders. In pateints with ER positive disease, 23 (64%) were responders. The most common toxicities were cytopenias and fatigue.ConclusionsNeoadjuvant S+T followed by AC+G-CSF was safe and tolerable in LABC and IBC. The study did not meet the prespecified endpoint for pCR; however, 47% were responders using pCR and/or CPS + EG score ≤2. ER positive patients had the highest response rate (64%). The addition of sunitinib to neoadjuvant chemotherapy may provide promising incremental benefit for patients with ER positive LABC.     

Pathologic complete response to neoadjuvant chemotherapy with trastuzumab predicts for improved survival in women with HER2-overexpressing breast cancer

BackgroundWe sought to determine the prognostic value of pathologic response to neoadjuvant chemotherapy with concurrent trastuzumab.Patients and methodsTwo hundred and twenty-nine women with HER2/neu (HER2)-overexpressing breast cancer were treated with neoadjuvant chemotherapy plus trastuzumab between 2001 and 2008. Patients were grouped based on pathologic complete response (pCR, n = 114) or less than pCR (<pCR, n = 115); as well as by pathologic stage. Locoregional recurrence-free (LRFS), distant metastasis-free (DMFS), recurrence-free (RFS), and overall survival (OS) rates were compared.ResultsThe median follow-up was 63 (range 53–77) months. There was no difference in clinical stage between patients with pCR or <pCR. Compared with patients achieving <pCR, those with the pCR had higher 5-year rates of LRFS (100% versus 95%, P = 0.011), DMFS (96% versus 80%, P < 0.001), RFS (96% versus 79%, P < 0.001), and OS (95% versus 84%, P = 0.006). Improvements in RFS and OS were seen with decreasing post-treatment stage. Failure to achieve a pCR was the strongest independent predictor of recurrence (hazard ratio [HR] = 4.09, 95% confidence interval [CI]: 1.67–10.04, P = 0.002) and death (HR = 4.15, 95% CI: 1.39–12.38, P = 0.011).ConclusionspCR and lower pathologic stage after neoadjuvant chemotherapy with trastuzumab are the strongest predictors of recurrence and survival and are surrogates of the long-term outcome in patients with HER2-overexpressing disease.     

Integrated evaluation of PAM50 subtypes and immune modulation of pCR in HER2-positive breast cancer patients treated with chemotherapy and HER2-targeted agents in the CherLOB trial

BackgroundThe aim of this work was to evaluate the impact of (and relative contribution of) tumor-related and immune-related diversity of HER2-positive disease on the response to neoadjuvant chemotherapy plus anti-HER2 agents.Patients and methodsThe CherLOB phase II study randomized 121 HER2-positive breast cancer patients to neoadjuvant chemotherapy plus trastuzumab, lapatinib or both. Tumor samples from diagnostic core biopsy were centralized. Tumor-infiltrating lymphocytes (TILs) were evaluated on H&E slides. Intrinsic subtyping was carried out using the research-based 50-gene prediction analysis of a microarray (PAM50) subtype predictor. Immune-related gene signatures were also evaluated.ResultsContinuous Str-TILs and It-TILs were significantly associated with pCR [OR 1.03, 95% CI 1.02–1.05 (P < 0.001) and OR 1.09, 95% CI 1.04–1.15 (P < 0.001) for Str-TILs and It-TILs, respectively]. According to PAM50, the subtype distribution was as follows: HER2-enriched 26.7%, Luminal A 25.6%, Luminal B 16.3%, Basal-like 14% and Normal-like 17.4%. The highest rate of pCR was observed for the HER2-enriched subtype (50%), followed by Basal-like, Luminal B and Luminal A (χ² test, P = 0.026). Immune gene signatures significantly associated with pCR in univariate analyses were identified: most of them maintained a significant association with pCR in multivariate analyses corrected for PAM50 subtypes, whereas TILs did not.ConclusionsIn this study, both tumor-related and immune-related features contribute to the modulation of pCR after neoadjuvant chemotherapy plus anti-HER2 agents. Immune signatures rather than TILs added significant prediction of pCR beyond PAM50 intrinsic subtypes.     

Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2‐positive breast cancer

BACKGROUND:

The axillary pathologic complete response rate (pCR) and the effect of axillary pCR on disease‐free survival (DFS) was determined in patients with HER2‐positive breast cancer and biopsy‐proven axillary lymph node metastases who were receiving concurrent trastuzumab and neoadjuvant chemotherapy. The use of neoadjuvant chemotherapy is reported to result in pCR in the breast and axilla in up to 25% of patients. Patients achieving a pCR have improved DFS and overall survival. To the authors' knowledge, the rate of eradication of biopsy‐proven axillary lymph node metastases with trastuzumab‐containing neoadjuvant chemotherapy regimens has not been previously reported.

METHODS:

Records were reviewed of 109 consecutive patients with HER2‐positive breast cancer and axillary metastases confirmed by ultrasound‐guided fine‐needle aspiration biopsy who received trastuzumab‐containing neoadjuvant chemotherapy followed by breast surgery with complete axillary lymph node dissection. Survival was evaluated by the Kaplan‐Meier method. Clinicopathologic factors and DFS were compared between patients with and without axillary pCR.

RESULTS:

Eighty‐one patients (74%) achieved a pCR in the axilla. Axillary pCR was not associated with age, estrogen receptor status, grade, tumor size, initial N classification, or median number of lymph nodes removed. More patients with an axillary pCR also achieved a pCR in the breast (78% vs 25%; P < .001). At a median follow‐up of 29.1 months, DFS was significantly greater in the axillary pCR group (P = .02).

CONCLUSIONS:

Trastuzumab‐containing neoadjuvant chemotherapy appears to be effective in eradicating axillary lymph node metastases in the majority of patients treated. Patients who achieve an axillary pCR are reported to have improved DFS. The success of pCR with concurrent trastuzumab and chemotherapy in eradicating lymph node metastases has implications for surgical management of the axilla in these patients. Cancer 2010. © 2010 American Cancer Society.     

Disease-free and overall survival at 3.5 years for neoadjuvant bevacizumab added to docetaxel followed by fluorouracil,epirubicin and cyclophosphamide,for women with HER2 negative early breast cancer: ARTemis Trial

BackgroundThe ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review.Patients and methodsPatients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class.ResultsA total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2–4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89–1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90–1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23–0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24–0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group.ConclusionsThe addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer.ClinicalTrials.gov numberNCT01093235.     

系统免疫炎症指数对激素受体阴性乳腺癌新辅助化疗后病理完全缓解的预测价值

目的:探讨化疗前系统免疫炎症指数(systemic immune-inflammation index, SII)与激素受体阴性乳腺癌新辅助化疗(neoadjuvant chemotherapy, NAC)后病理完全缓解(pathological complete response, pCR)的关系。方法:回顾性分析2013年1月-2017年1月在我院接受新辅助化疗并行手术的278例女性乳腺癌临床病理资料,组间分析通过Pearson’sχ²进行评估。使用Logistic回归模型进行单因素和多因素分析。结果:本研究共91例(32.7%)患者接受新辅助化疗后获得pCR,其中低SII组55例,高SII组36例,SII与pCR相关(P=0.015)。单因素分析显示：T₁+T₂组(pCR率37.10%)较T₃+T₄组(pCR率15.79%)更易获得pCR(P=0.003);低SII组(pCR率39.57%)较高SII组(pCR率25.90%)更易获得pCR(P=0.016);将单因素分析...