Neoadjuvant docetaxel and capecitabine (TX) versus docetaxel and epirubicin (TE) for locally advanced or early her2-negative breast cancer: an open-label, randomized, multi-center, phase II Trial.

PURPOSE: The combination of taxanes and anthracyclines is still the mainstay of chemotherapy for early breast cancer. Capecitabine is an active drug with a favorable toxicity profile, showing strong anti-tumor activity against metastatic breast cancer. This trial assessed the efficacy and safety of the TX regimen (docetaxel and capecitabine) and compared it with the TE (docetaxel and epirubicin) regimen in locally advanced or high risk early HER2-negative breast cancer. PATIENTS AND METHODS: This randomized clinical trial was conducted at five academic centers in China. Eligible female patients were randomly assigned (1:1) to the TX (docetaxel 75 mg/m2 d1 plus capecitabine 1000 mg/m2 twice d1-14, q3w) or TE (docetaxel 75 mg/m2 d1 plus epirubicin 75 mg/m2 d1, q3w) groups for four cycles. The primary endpoint was a pathological complete response in the breast (pCR). Secondary endpoints included pCR in the breast and axilla, invasive disease-free survival (iDFS), overall survival (OS), and safety. RESULTS: Between September 1, 2012, and December 31, 2018, 113 HER2-negative patients were randomly assigned to the study groups (TX: n = 54; TE: n = 59). In the primary endpoint analysis, 14 patients in the TX group achieved a pCR, and nine patients in the TE group achieved a pCR (25.9% vs. 15.3%), with a not significant difference of 10.6% (95% CI -6.0-27.3%; P = 0.241). In a subgroup with high Ki-67 score, TX increased the pCR rate by 24.2% (95% CI 2.2-46.1%; P = 0.029). At the end of the 69-month median follow-up period, both groups had equivalent iDFS and OS rates. TX was associated with a higher incidence of hand-foot syndrome and less alopecia, with a manageable toxicity profile. CONCLUSION: The anthracycline-free TX regimen yielded comparable pCR and long-term survival rates to the TE regimen. Thus, this anthracycline-free regimen could be considered in selected patients. TRIAL REGISTRATION: ACTRN12613000206729 on 21/02/2013, retrospectively registered.

Application of the ACOSOG Z0011 criteria to Chinese patients with breast cancer: a prospective study.

BACKGROUND: Although the ACOSOG Z0011 study showed that axillary lymph node dissection (ALND) could be avoided in a specific population of sentinel lymph node-positive patients, it is not widely accepted by Chinese surgeons. We conducted a prospective single-arm study to confirm whether or not the results of Z0011 are applicable to Chinese patients. METHODS: Patients conforming to the Z0011 criteria were prospectively enrolled at the Peking University People's Hospital Breast Center from November 2014 to June 2019. The clinicopathological features of the study group were compared with those of the Z0011 study group. Lymphedema after surgery, the incidence of local-regional recurrence, and survival were analyzed. RESULTS: One hundred forty-two patients who met the Z0011 eligibility criteria were enrolled in this study; 115 underwent sentinel lymph node biopsy (SLNB) alone. Compared with the Z0011 trial, younger patients were included (median age, 52 [26-82] years vs 54 [25-90] years; P = 0.03). For clinical T stage, tumor histology, hormone status, lymphovascular invasion, and the number of positive sentinel lymph nodes (SLNs), no statistically significant differences were observed. More patients received adjuvant chemotherapy and endocrine therapy in this study (90.85% vs 58.0% and 80.99% vs 46.6% respectively, P <0.001). A similar percentage of patients received radiotherapy, but more nodal radiotherapy procedures were carried out in our study (54.5% vs 16.9%). After a median follow-up of 29 months, only 1 patient (0.9%) had ipsilateral breast tumor recurrence, and no regional recurrence occurred. CONCLUSION: Our study showed that it is achievable to avoid ALND in patients eligible for Z0011 in China. TRIAL REGISTRATION: ClinicalTrials.gov. Registration number NCT03606616 . Retrospectively registered on 31 July 2018.

Long-term follow-up results of fluorescence and blue dye guided sentinel lymph node biopsy in early breast cancer.

PURPOSE: This study aimed to assess the efficacy of the combination of indocyanine green (ICG) and methylene blue (MB) dye in early breast cancer patients undergoing sentinel lymph node biopsy (SLNB). METHODS: Between January 2011 and December 2015, 1061 early breast cancer patients underwent SLNB were included. SLNB was performed for enrolled patients by injection of both ICG and MB. Detection rate, positivity, and number of sentinel lymph nodes (SLNs) by ICG and MB were analysed. Axillary recurrence and arm lymphedema at 5.6-year follow-up were reported. RESULTS: The combination of ICG and MB resulted in a very high detection rate of 99.6%, the median number of sentinel lymph nodes was 3. A total of 374 histologically confirmed positive SLNs were detected in 237 patients, 96.6% of the positive patients and 94.1% of the positive nodes could be identified by the combination of ICG and MB. After a median follow-up of 5.6 (2-9.3) years, 0.64% of patients with negative SLNs had ipsilateral axillary recurrence, and the incidence of arm lymphedema was 2.1%. CONCLUSIONS: Although the missing isotope control weakens the interpretation of the findings, the dual tracing modality of ICG and MB, without involvement of radioactive isotopes, was an effective method for SLNB in patients with early breast cancer. TRIAL REGISTRATION: ACTRN12612000109808. Registered on 23 January 2012.

Evaluating and Balancing the Risk of Breast Cancer-Specific Death and Other Cause-Specific Death in Elderly Breast Cancer Patients.

Purpose: The dilemma of undertreatment and overtreatment of elderly breast cancer patients is common. This study aimed to investigate clinicopathological features, treatment modalities, and survival in women diagnosed with breast cancer at age 70 years or over, and to assist clinicians in developing individualized treatment plans by balancing the risks of breast cancer-specific death (BCSD) and other cause-specific death (OCSD). Methods: This retrospective study included 420 women who were diagnosed with pathologically confirmed invasive breast cancer at age 70 years or older from January 2008 to December 2015 at Peking University People's Hospital (PKUPH). We collected baseline health status, tumor characteristics, treatment choices, and outcomes and created nomograms for clinicians to estimate individualized BCSD and OCSD risk directly. Results: During a median follow-up of 71.5 months (range 2 to 144 months) in patients with stage I-III tumors, breast cancer specific survival (BCSS) was 92.4% (376/407) and overall survival (OS) was 78.1% (318/407). There were 89 deaths, and 65.2% (58/89) were non-breast cancer related. Upon multivariate analysis by Cox regression model, tumor size, positive lymph nodes, Ki-67, and surgery were independent predictors of BCSS, and comorbidities, positive lymph nodes, Ki-67, surgery, and endocrine therapy were independent predictors of OS. Propensity score weighted (PSW) was applied to analyze therapeutic efficacy, and there was BCSS and OS benefit with surgery (both p < 0.001), BCSS benefit with chemotherapy (p = 0.029), BCSS and OS benefit with endocrine therapy (p = 0.006 and 0.004), and neither BCSS nor OS benefit with radiotherapy (RT) (p = 0.348 and 0.289). Competing-risk nomograms were developed to estimate cumulative mortality probabilities for BCSD and OCSD for individual patients according to clinicopathologic characteristics and treatments. The calibration curves displayed exceptionally, with C-indexes 0.714 for BCSD and 0.717 for OCSD. Conclusions: Older patients had greater risk of dying from non-breast cancer causes. Surgery, chemotherapy, and endocrine therapy were associated with improved survival. Competing risk nomograms allowed individual assessment of BCSD and OCSD, based on clinicopathological characteristics and treatment options, and can be used as a tool to help in choosing appropriate treatment strategies. This study was approved by the Peking University People's Hospital Research Ethics Board on September 4, 2018.

Use of high-resolution full-field optical coherence tomography and dynamic cell imaging for rapid intraoperative diagnosis during breast cancer surgery.

BACKGROUND: Although traditional intraoperative assessments (ie, frozen sections) may lower reoperation rates in patients with breast cancer, time/tissue limitations and accuracy concerns have discouraged their routine clinical use. Full-field optical coherence tomography (FFOCT) and dynamic cell imaging (DCI) are novel optical imaging techniques offering rapid histologic approximations that are unfettered by requisite handling steps. This study was conducted to determine the feasibility and diagnostic utility of FFOCT and DCI in examining breast and lymph node specimens during breast cancer surgery. METHODS: FFOCT and DCI were applied to normal and cancerous breast tissue, benign breast lesions, and resected axillary lymph nodes. The tissues were then subjected to conventional processing and staining (hematoxylin-eosin) for purposes of comparison. RESULTS: A total of 314 specimens, including 173 breast biopsies (malignant, 132; benign/normal, 41) and 141 resected lymph nodes (tumor-positive, 48; tumor-negative, 93), were obtained from 158 patients during breast surgery for prospective imaging evaluations. In breast cancer diagnosis, the minimum sensitivities (FFOCT, 85.6%; DCI, 88.6%) and specificities of optical imaging (FFOCT, 85.4%; DCI, 95.1%) were high, although they diverged somewhat in nodal assessments (FFOCT sensitivity, 66.7%; FFOCT specificity, 79.6%; DCI sensitivity, 83.3%; DCI specificity, 98.9%). CONCLUSIONS: These timely and tissue-sparing optical imaging techniques proved highly accurate in diagnosing breast cancer and nodal metastasis. They compare favorably with routine histologic sections and demonstrate their promise in this setting.

Lymph Node Predictive Model with in Vitro Ultrasound Features for Breast Cancer Lymph Node Metastasis.

Ultrasound diagnosis of axillary lymph nodes has the advantages of ease, convenience and low cost; however, most previous studies evaluated lymph node metastasis of the entire axilla rather than the association between the ultrasound features of a single lymph node and its pathology. This prospective study was performed to explore the ultrasound features of lymph nodes observed in bionic medium in vitro and to develop a lymph node-specific model for prediction of metastasis based on analysis of the association between the ultrasound features and pathology of each lymph node. From November 1, 2017 to December 19, 2017, 373 nodes (54 patients) were enrolled into the modeling group; from December 20, 2017 to January 12, 2018, 139 lymph nodes (22 patients) were enrolled into the validation group. Lymph nodes from sentinel lymph node biopsy or axillary lymph node dissection were enrolled. Individual lymph nodes were placed in bionic medium and observed separately using ultrasound. Traditional ultrasound features of metastatic nodes (long axis, short axis, cortical thickness and hilum loss) were recorded, and the longitudinal-to-transverse axis ratio (L/T) and cortical proportion were calculated. Pathologic results specific to each lymph node were recorded. On the basis of two-level binary logistic regression, independent predictors of lymph node metastasis in the modeling group were lymph node long axis (p = 0.004), short axis (p < 0.001), L/T (p = 0.006), cortical thickness (p = 0.001) and hilum loss (p < 0.001). When analysis was done at the node level, the areas under the curve of the modeling and validation groups were 0.97 and 0.75, respectively. When validation was done at the patient level, the areas under the curve of the modeling and validation groups were 0.96 and 0.93, respectively. The model for prediction of metastasis based on the ultrasound features and pathology of each lymph node is of good predictive value for lymph node metastasis.

Retrospective analysis of concurrent docetaxel and epirubicin neoadjuvant versus adjuvant chemotherapy: Which leads to better outcomes for different subtype breast cancer patients?

Different biological subtype breast cancers respond differently to neoadjuvant chemotherapy, but it is unknown whether neoadjuvant or adjuvant chemotherapy leads to different long-term survival in each specific subtype although equal outcomes have been reported in general population. This study sought to clarify whether the selection of either neoadjuvant or adjuvant chemotherapy was linked to a differential survival benefit based on breast cancer subtypes.A prospectively maintained breast cancer database was queried from 2000 to 2008. All patients with a diagnosis of stage II and III breast cancer who received neoadjuvant or adjuvant chemotherapy were identified, only patients receiving docetaxel and epirubicin (TA) regimen were included. Patients were divided according to the administration of neoadjuvant or adjuvant chemotherapy. The biological subtypes were determined by immunohistochemical tests. The outcomes between neoadjuvant and adjuvant chemotherapy were compared in each different subtype. Kaplan-Meier curves were generated, and the Cox model was used to estimate the association between death risk and chemotherapy timing while adjusting for potentially confounding factors. P values < .05 were considered statistically significant.Of the 406 patients included, 201 (49.5%) received neoadjuvant chemotherapy, and 205 (50.5%) received an adjuvant TA regimen. Patients with the HER2+ and TNBC subtypes showed significantly higher pCR rates than patients with luminal types (P < .05). In general population, the neoadjuvant and adjuvant chemotherapy groups showed little survival variance (HR=1.15, 95% confidence interval (CI) .69-1.91, P=.60). In luminal B-like patients, neoadjuvant chemotherapy led to worse overall survival (OS) than adjuvant therapy (HR=2.92, 95%CI 1.20 to 8.31, P = .02). In patients with the HER2+ subtype, neoadjuvant treatment corresponded to better OS (HR = .10, 95%CI .02-.58, P = .01). In contrast, patients with luminal A-like (HR = 1.14, 95%CI .53-2.43, P = .74) and TNBC disease (HR = 1.00, 95%CI .27-3.73, P = >.99) who underwent neoadjuvant chemotherapy showed equivalent OS when compared to patients undergoing adjuvant therapy.Neoadjuvant versus adjuvant chemotherapy results in a disparate impact on overall survival among patients with variant subtype breast cancer. When neoadjuvant chemotherapy was given, luminal B-like patients showed worse outcome, while patients with HER2+ disease had better OS. Prospective studies are necessary to determine and optimize the timing of chemotherapy for breast cancers with different molecular backgrounds.

Comparison of sentinel lymph node biopsy guided by indocyanine green, blue dye, and their combination in breast cancer patients: a prospective cohort study.

BACKGROUND: Recent studies show that near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has the potential to improve the performance of sentinel lymph node (SLN) mapping. The current cohort study was designed to assess the value of the combination of ICG and methylene blue (MB) dye in patients undergoing SLN biopsy. METHODS: A prospective self-controlled trial was designed to detect the difference in the detection efficacies of ICG, MB, and combined ICG and MB (ICG + MB) navigation methods. Between 2010 and 2013, 198 consecutive early breast cancer patients eligible for sentinel lymph node biopsy were enrolled and 200 biopsy procedures were performed by injection of both ICG and MB. SLNs were searched and removed under the guidance of fluorescence and/or blue dye. The mapping characteristics, the detection rate of SLNs and positive SLNs, and the number of SLNs of ICG, MB, and ICG + MB were compared. Injection safety of ICG and MB was evaluated. RESULTS: Fluorescence imaging of lymphatic flow, which is helpful to locate the incision site, could be seen in 184 of 200 procedures. The nodal detection rate of ICG, MB, and ICG + MB samples was 97, 89, and 99.5% (χ 2 = 26.2, p < 0.001), respectively, with the combination method yielding a superior identification result. The addition of ICG to the MB method resulted in the identification of more lymph nodes (median 3 versus 2) and more positive axillas (22.7% involved axillas were discovered by fluorescence only) than either method alone. No acute or chronic allergic reaction was observed in this study. However, 23 patients (23/82) who received breast-conserving therapy reported temporary skin staining, and 5 patients had permanent tattooing. Palpable subcutaneous nodules at the injection sites were reported in nine patients. There were no reports of skin necrosis. CONCLUSIONS: The lymphatic navigation by ICG fluorescence detects SLNs at a high detection rate and improves the mapping performance when added to the MB method. The novel ICG + MB dual tracing modality, without involvement of radioactive isotopes, exhibits great potential as an alternative to traditional standard mapping methods. TRIAL REGISTRATION: ACTRN12612000109808 . Retrospectively registered on 23 January 2012.

Intradermal microbubbles and contrast-enhanced ultrasound (CEUS) is a feasible approach for sentinel lymph node identification in early-stage breast cancer.

BACKGROUND: Microbubbles and contrast-enhanced ultrasound (CEUS) is a new technique for locating sentinel lymph node (SLN). The aim of this study is to explore the feasibility of SLNs tracing by CEUS using microbubbles in breast cancer patients and the value of enhancing patterns in diagnosing lymph nodes metastases. METHODS: A clinical trial was registered (trial registration: ChiCTR-DDT-13003778). One hundred and one consecutive consenting patients with breast cancer undergoing SLN biopsy were enrolled. Before the surgery, microbubble was injected periareolarly. Lymphatic drainage pathway was detected by CEUS, and guidewire was deployed to locate the SLN before the operation. Blue dye was also used to help in tracing sentinel lymph node during the operation. The identification rate and the accuracy rate were recorded. Enhancing patterns of lymph nodes were recorded and compared with the pathological diagnosis. RESULTS: Of the 101 cases, SLNs in 99 cases were successfully identified by at least one tracer, including 98 cases identified by CEUS and 97 cases by blue dye. There was no significant difference between the two methods (P = 0.705). Guidewires were deployed successfully in all 98 cases, and the localized SLNs were all isolated successfully in the following operations. The status of SLNs isolated by CEUS was completely identical to that of the whole axillary lymph node while 7.1 % cases were misdiagnosed as negative by blue dye method. The sensitivity of predicting SLNs metastases by CEUS enhancing pattern was 81.8 %, the specificity was 86.2 %, and the positive and negative predictive values were 75.0 and 90.3 %, respectively. CONCLUSIONS: Microbubbles and CEUS are feasible approaches for SLN identification. The enhancing patterns on CEUS may be helpful to recognize the metastasizing SLNs. This novel method may be a promising technique for the clinical application.

A logistic regression model for predicting axillary lymph node metastases in early breast carcinoma patients.

Nodal staging in breast cancer is a key predictor of prognosis. This paper presents the results of potential clinicopathological predictors of axillary lymph node involvement and develops an efficient prediction model to assist in predicting axillary lymph node metastases. Seventy patients with primary early breast cancer who underwent axillary dissection were evaluated. Univariate and multivariate logistic regression were performed to evaluate the association between clinicopathological factors and lymph node metastatic status. A logistic regression predictive model was built from 50 randomly selected patients; the model was also applied to the remaining 20 patients to assess its validity. Univariate analysis showed a significant relationship between lymph node involvement and absence of nm-23 (p = 0.010) and Kiss-1 (p = 0.001) expression. Absence of Kiss-1 remained significantly associated with positive axillary node status in the multivariate analysis (p = 0.018). Seven clinicopathological factors were involved in the multivariate logistic regression model: menopausal status, tumor size, ER, PR, HER2, nm-23 and Kiss-1. The model was accurate and discriminating, with an area under the receiver operating characteristic curve of 0.702 when applied to the validation group. Moreover, there is a need discover more specific candidate proteins and molecular biology tools to select more variables which should improve predictive accuracy.

Response to neoadjuvant therapy and disease free survival in patients with triple-negative breast cancer.

BACKGROUND: Triple negative breast cancer(TNBC)is characterized by estrogen receptor (ER) negative, progesterone receptor (PgR)negative and human epidermal growth factor receptor 2 (HER-2) negative. It is a high risk breast cancer that lacks the benefit of specific therapy targeting these proteins. In this study, we compared the response to neoadjuvant chemotherapy and disease free survival between patients with TNBC and non-TNBC. METHODS: 151 patients were included in this study, who received neoadjuvant taxane and anthracycline-based chemotherapy at Peking University People's Hospital from 2002 to 2007. TNBC is defined by the lack of ER, PgR, and HER-2 expression by immunohistochemistry. Clinical and pathologic parameters, pathologic complete response(pCR)rates and survival measurements were compared between patients with TNBC and non-TNBC. RESULTS: 21 of 151 patients (14%) had TNBC. Patients with TNBC compared with non-TNBC had significantly higher pCR rates(38% v 12%; p=0.002), but decreased disease-free survival rates(p=0.004). If pCR was achieved, patients with TNBC and non-TNBC had similar survival (p=0.497). CONCLUSIONS: Patients with TNBC have increased pCR rates compared with non-TNBC, and those with pCR achieved excellent disease free survival. However, patients who did not get pCR have significantly worse survival if they have TNBC compared with non-TNBC.

[The effect of neoadjuvant chemotherapy on estrogen and progesterone receptor expression in breast carcinoma].

OBJECTIVE: To investigate the effect of neoadjuvant chemotherapy on estrogen receptor (ER) and progesterone receptor (PR) expression in breast carcinoma. METHODS: Samples were obtained from 31 patients with breast carcinoma who received neo-adjuvant chemotherapy, ER or PR expressions were analyzed in preoperative core biopsies and final surgical specimens. RESULTS: ER level was up-regulated in 13 (41.9%) out of 31 cases, PR level was up-regulated in 10 (32.3%). Both ER level and PR level were up-regulated in 8 (25.8%) out of 31 cases. CONCLUSIONS: Neoadjuvant chemotherapy may impact the hormone receptor status, ER and PR expression re-analysis in final surgical specimens is recommended.

[Feasibility of breast conservation surgery after neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To investigate the efficacy of neoadjuvant chemotherapy (NCT) and the feasibility of conservative breast surgery after reducing the size of a primary tumor by NCT in patients with operable breast cancer. METHODS: Thirty patients with stage IIB and IIIA breast cancer underwent NCT including epirubicin 60 mg/m(2) by intravenous injection on day 1 and paclitaxel 150 mg/m(2) by 3-hour continuous infusion on day 2 with 21 days as a cycle from July 2001 to April 2003. All patients received 3 - 4 cycles of NCT. Breast conservation treatment or modified mastectomy was performed after the tumor was reduced to less than 3 cm in diameter. The nonresponders received modified mastectomy. RESULTS: The overall response rate (ORR) was 93% (28/30) for the primary tumors of breast, Fifteen patients (50%) obtained clinical complete response (cCR), including 7 cases (23%) with pathologic complete response (pCR). Thirteen cases (43%) achieved clinical partial response (cPR), and 2 (7%) no change (NC). No case showed progression of disease. Twenty-six (87%) cases were downstaged according to the TNM system classification. The median initial tumor size was 4 cm (3 - 10 cm) before NCT and was reduced to 0.8 cm (0 - 6 cm) after NCT. All 30 patients received operation. Eighteen (60%) of them were candidates for breast conserving therapy, and actually only 11 (37%) selected such surgery. CONCLUSION: An effective treatment for operable breast cancer, NCT with epirubicin plus paclitaxel results in significant downstaging or eliminating of primary tumors in breast cancer, thus expanding the indication of breast conservation therapy.

[Expression and significance of estrogen receptor isoforms in the development of human breast carcinoma].

OBJECTIVE: To investigate the estrogen receptors (ER)alpha and ERbeta expression and their relationship with clinicopathological parameters in human breast carcinoma. METHODS: Samples were obtained from 30 breast carcinoma, reverse transcriptase polymerase chain reaction was used to measure the expression of ERalpha and ERbeta mRNA. RESULTS: ERalpha mRNA level was up-regulated in breast carcinoma tissue compared with adjacent normal tissue (t = 7.399, P < 0.01) while down-regulated in ERbeta. The relative ratio of ERalpha and ERbeta was decreased in normal tissue vs. carcinoma (t = 6.385, P < 0.01), in patients with lymph node metastasis vs. those without lymph node metastasis (t = 2.602, P < 0.05), in late stage carcinoma vs. early stage (t = 3.754, P < 0.05). CONCLUSION: ERalpha and ERbeta play divergent role in the development of human breast carcinoma.

[Clinical evaluation of effects from neoadjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer--comparative study of treatment with 2 and 4 cycles].

Neoadjuvant chemotherapy of epirubicin plus paclitaxel was administered to 75 patients (including a 2-cycle group of 39 patients and a 4-cycle group of 36 patients) with locally advanced breast cancer (35 cases of stage IIb, 28 of stage IIIa, 12 of stage IIIb) to compare efficacy and toxicity of 2 cycle and 4 cycle regimens. All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v., followed by paclitaxel 150 mg/m2, by 3 hour continuous infusion on day 2 repeated every 3 weeks. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteritic and allergic reactions before chemotherapy. Thirty-nine patients were given 2 cycles and thirty-six were given 4 cycles of this regimen. One of 39 patients had complete response, 28 had partial response and 10 had no change in the 2-cycle group. In addition, 21 of 36 patients had complete response (including 9 who had pathologic complete response), 13 had partial response and 2 had no change. The response rates were 74% (29/39) in the 2-cycle group and 94% (34/36) in the 4-cycle group. There were no progressive disease in these 2 groups. However a higher proportion of PR was observed in stage II patients than in stage III patients. Twelve of 36 patients underwent breast conserving surgery, as tumor size had become smaller and down-staging was realized after neoadjuvant chemotherapy. In addition, axillary lymph nodes were palpable in all 75 patients before neoadjuvant chemotherapy with the ET regimen. But 46% (18/39) in the 2-cycle group and 75% (27/36) in the 4-cycle group became impalpable. Conversely, major toxicities (including leukopenia and gastroenteric reactions) were similar in both groups, but myalgia, arthralgia, neurotoxicity and alopecia were more severe in the 4-cycle group than in the 2-cycle group. In the present study, neoadjuvant chemotherapy with a 4-cycle ET regimen was more effective than with a 2-cycle regimen in down staging locally advanced breast cancer. Although major toxicities were more severe in the 4-cycle group than in the 2-cycle group, the regimen was tolerable and safe.

[Clinical evaluation of effects from neo-adjuvant chemotherapy with epirubicin plus paclitaxel in cases of locally advanced breast cancer].

Neo-adjuvant chemotherapy of epirubicin plus paclitaxel was administered to 23 patients with locally advanced breast cancer (including 13 cases of stage IIb, 6 of stage IIIa, and 4 of stage IIIb). All patients were female. They were treated with epirubicin 60 mg/m2, on day 1, by i.v. followed paclitaxel 150 mg/m2 by 3 hours continuous infusion on day 2 and every 3 weeks repeatedly. Premedication with dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Two to 4 cycles were used. Ten out of 23 patients had a complete response, 10 had partial response, and 3 had no change. The response rate was 87% (20/23). Six out of 23 patients underwent breast conserving surgery as tumor size had become smaller and downstaging was realized after neo-adjuvant chemotherapy. The major toxicities included neutropenia, myalgia, arthralgia, nephrotoxicity, gastroenteric reactions, alopecia and flushing to the face. However, these were well tolerated in these patients.

[Evaluation of two different regimens as neoadjuvant chemotherapy for breast cancer].

OBJECTIVE: To compare the efficacy and toxicity of two different regimens as neoadjuvant chemotherapy for breast cancer. METHODS: Forty-eight patients with stage II, III breast cancer as proved by cytology biopsy, were treated with either 5-Fu, epirubicin, cyclophosphamide (FEC) or epirubicin, paclitaxel (ET) regimens for 2 cycles every 3 - 4 weeks. Clinical responses in the breast and lymph nodes were assessed after 2 cycles of neoadjuvant chemotherapy. Patients in FEC arm received combination of 5-fluorouracil (5-Fu) 500 mg/m(2) by 4-hour continuous infusion on D1 and D8, epirubicin (EPI) 50 mg/m(2) by intravenous injection on D1, and cyclophosphamide (CTX) 500 mg/m(2) by intravenous injection on D1 and D8. Patients assigned to the ET arm received EPI 60 mg/m(2) by intravenous injection on D1, paclitaxel (TAX) 150 mg/m(2) by 3-hour continuous infusion on D2. All patients were treated by operation 2 weeks later and radiotherapy was added to some. RESULTS: For primary tumor in the breast, the overall response rate (RR) was 50.0% (12/24) in FEC arm and 79.2% (19/24) in ET arm. One patient showed clinical complete response (cCR), 11 partial response (PR), 12 no change (NC) after the FEC therapy, while 1 patient showed CR, 18 PR, 5 NC after ET therapy. There was no pathologic complete response or progressive disease, though a higher proportion of RR was observed in stage II than stage III patients in these two groups. Clinically palpable axillary lymph nodes which had been found in all 48 patients before 2 cycles of treatment, 50.0% (12/24) in the FEC patients and 66.7% (16/24) in the ET patients became in-palpable. The major toxicity, including leukopenia, gastroenteric reactions, were similar in both groups, but alopecia was more severe and arthralgia, myalgia, neurotoxicity and flushing of face were the unique features of the ET regimen. CONCLUSION: Neoadjuvant chemotherapy with two different regimens were effective to the primary tumor and axillary metastatic lymph nodes of breast cancer, and the side effects were tolerable. Higher efficacy and more side effects are observed in ET than in FEC regimen.