Influence of Biologic Subtype of Inflammatory Breast Cancer on Response to Neoadjuvant Therapy and Cancer Outcomes

Background

Few data exist on the influence of tumor biologic subtype on treatment response and outcomes for inflammatory breast cancer (IBC). We examined a contemporary cohort of IBC patients treated with current targeted systemic therapies, selected on the basis of tumor biologic subtype, to evaluate pathologic treatment response and cancer outcomes across biologic subtypes.

Risk Factors for Locoregional Failure in Patients With Inflammatory Breast Cancer Treated With Trimodality Therapy

PurposeTo compare patterns of local and regional failure between patients with inflammatory breast cancer (IBC) and non-IBC in patients treated with trimodality therapy.Materials and MethodsWe reviewed records of 463 patients with stage II/III breast cancer, including IBC, who completed trimodality therapy from January 1999 to December 2009.ResultsThe median follow-up was 46.3 months (range, 4-152 months). Clinical stage was 29.4% (n = 136) II, 56.4% (n = 261) non-IBC III, 14.2% (n = 66) IBC, 30.5% (n = 141) cN0/Nx, and 69.5% (n = 322) N1-N3c. All the patients received neoadjuvant therapy and mastectomy (98%, n = 456 with axillary dissection), and all had postmastectomy radiation therapy to the chest wall with or without supraclavicular nodes (82.5%, n = 382) with or without axilla (6%, n = 28). The median chest wall dose was 60.4 Gy. Patients with IBC presented with larger tumors (P < .001) and exhibited a poorer response to neoadjuvant therapy: after surgery, fewer patients with IBC were ypN0 (P = .003) and more had ≥ 4 positive nodes (P < .001). Four-year cumulative incidence of locoregional recurrence was 5.9%, with 25 locoregional events, 9 of which had a regional component. On multivariate analysis, triple-negative disease (hazard ratio [HR] 7.75, P < .0001) and residual pathologic nodes (HR 7.10, P < .001) were associated with an increased risk of locoregional recurrence, but IBC was not. However, on multivariate analysis, the 4-year cumulative incidence of regional recurrence specifically was significantly higher in IBC (HR 9.87, P = .005).ConclusionIn this cohort of patients who completed trimodality therapy, the patients with IBC were more likely to have residual disease in the axilla after neoadjuvant therapy and were at greater risk of regional recurrence. Future study should focus on optimizing regional nodal management in IBC.     

Neoadjuvant Intra-arterial Chemotherapy in Locally Advanced Breast Cancer: A Prospective Randomized Study

A prospective randomized study of neoadjuvant chemotherapy wascarried out on 73 patients with locally advanced breast cancer.Group A (n 26) received no neoadjuvant therapy, group B (n 22)received intra-arterial infusions of epirubicin and group C(n 25) received intravenous epirubicin. The regression of theprimary tumor was significantly higher in group B than in groupC (68.2 vs 36.0%, P<0.05). The post-operative survival ofresponders to neoadjuvant therapy was better than that of non-responders.Side effects were milder in group B than in group C. There was,however, no difference among the three groups in terms of overalland disease-free survivals. Thus, neoadjuvant intra-arterialchemotherapy was effective for achieving loco-regional controlof locally advanced breast cancer with a low toxicity, but couldnot improve survival.     

Neoadjuvant Chemotherapy for Locally Advanced Breast Cancer in a Malaysian Tertiary Hospital

Introduction: Neoadjuvant chemotherapy for locally advanced breast cancer is given with the aim of shrinkingthe disease sufficiently for surgery. However, many clinical trials investigating neoadjuvant chemotherapyregimens were conducted for operable breast cancer. Methods and Materials: Patients with T3-4, N2 M0 breastcancer diagnosed between January 2005 and December 2008 and who received at least one cycle of neoadjuvantchemotherapy were eligible for this study. Thirty-four patients were identified from the Chemotherapy DaycareRecords and their medical records were reviewed retrospectively. The neoadjuvant chemotherapy regimenadministered was at the discretion of the treating oncologist. Breast tumour size and nodal status was assessedat diagnosis, at each cycle and before surgery. Results: All 34 patients had invasive ductal cancer. The medianage was 52 years (range 27-69). 65% had T4 disease and 76% were clinically lymph node positive at diagnosis.The median size of the breast tumour at presentation was 80 mm (range 42-200 mm). Estrogen and progesteronereceptor positivity was seen in less than 40% and HER2 positivity, by immunohistochemistry, in 27%. Themajority (85%) of patients had anthracycline based chemotherapy, without taxanes. The overall response rate(clinical CR+PR) was 67.6% and pathological complete responses were apparent in two (5.9%). 17.6% ofpatients defaulted part of their planned treatment. Recurrent disease was seen in 44.1% and the median time torelapse was 11.3 months. The three year disease free and overall survival rates were 52.5% and 58% respectively.Conclusion: Neoadjuvant chemotherapy for locally advanced breast cancer in a Malaysian setting confersresponse and pCR rates comparable to published clinical trials. Patients undergoing neoadjuvant chemotherapyare at risk of defaulting part of their treatment and therefore their concerns need to be identified proactivelyand addressed in order to improve outcomes.     

术前化疗与乳腺癌多药耐药的关系

目的：了解可手术的乳腺癌对术前化疗的反应性以及与多药耐药的关系，探讨其机制。方法：将80例Ⅱ期乳腺癌患者随机分为2组，即术前未化疗组和CMF方案化疗组；分别观察其多药耐药基因蛋白（P－gp)的表达情况及与化疗反应的关系，并观察肿瘤体外药敏试验的耐药情况。结果：本组化疗部分缓解和轻度缓解分别为12／40（30．0％）、21／40（52．5％）；未化疗组P－gp表达率为22．5％，经化疗后表达率明显升高（P＜0．05）；对化疗有较好反应的肿瘤，其P－gp多为阳性表达。体外药敏试验显示化疗后肿瘤细胞对长春碱类及蒽环类的耐药比率明显增加（P＜0．05）。结论：术前CMF方案化疗有一定疗效，经化疗后残留癌细胞的P－gp表达增加，可能出现交叉耐药性，术后可参考药敏试验选择化疗药物。     

Intraoperative Touch Imprint Cytology in Breast Cancer Patients After Neoadjuvant Chemotherapy

BackgroundIntraoperative touch imprint cytology (ITIC) is used for intraoperative detection of sentinel lymph node (SLN) metastases with intention to spare the patients another surgery. However, ITIC prolongs surgery, and ads costs. It is less likely positive in breast cancer (BC) patients after neoadjuvant chemotherapy (NAC) due to low axillary tumor burden. We aimed to evaluate ITIC in patients after NAC and assess how often it changes the ongoing surgery.Materials and MethodsBC patients treated with NAC followed by surgery at the Institute of Oncology Ljubljana, Slovenia, from January 2008 to July 2020 with ITIC performed were selected for analysis. Sensitivity, specificity, and the proportion of positive ITIC were calculated for different subgroups.ResultsOverall, 144 patients were identified. 73 of 144 (50.7%) patients were N0 before NAC and 71 of 144 (49.3%) were initially N1 and downstaged to N0 after NAC. ITIC was positive in 30 of 144 (20.8%) of patients, 7 of 73 (9.6%) in N0 group and 23 of 71 (32.4%) in N1 group. In N0 group, ITIC was positive in 1 of 20 (5%) if the tumor size was ≤ 20 mm after NAC, and 2 of 39 (5.1%) if the tumor was triple negative (TN) or Her-2+. In the N1 group ITIC was positive in > 20% in all subgroups. The sensitivity and specificity of ITIC was 50.8% and 100%, respectively and did not differ between groups.ConclusionITIC after NAC is accurate with comparable sensitivity to ITIC in upfront surgery. We suggest omission of ITIC after NAC in initially N0 patients, particularly for tumors ≤ 20 mm after NAC, and in TN or Her-2+ subtypes.     

Long-Term Follow-up of Immediate Latissimus Dorsi Flap Reconstruction After Neoadjuvant Chemotherapy and Radiotherapy for Invasive Breast Cancer

BackgroundThe treatment sequence involving a mastectomy and immediate breast reconstruction (IBR) via the latissimus dorsi flap technique after chemotherapy and radiotherapy is not common. Our experience of this alternative to the standard treatment at our institute is reported herein.Patients and MethodsThis was a single-center, retrospective study. We enrolled patients who received this so-called “inverse” sequence for invasive, nonmetastatic breast cancer between 2009 and 2016.ResultsFifty-two patients, aged between 24 and 65 years, with a mean body mass index of 24.5 underwent this treatment. Most involved T2 (59.6%, n = 32), multifocal (55.8%, n = 29) tumors, and 57.7% (n = 30) of the patients presented with axillary lymph node involvement. All patients had received sequential chemotherapy and 50 Gy of radiation. Pathological complete response (pCR) was found in 51.3% (n = 20), of cases in the traditional inverse sequence group, using Chevalier and Sataloff classifications (T and N pCR). Postoperatively, 1 patient required surgical revision because of a hematoma, 42 (80.8%) presented with lymphocele, 3 had impaired would healing, and 2 had more than 5 cm of skin necrosis on the front flap. Median follow-up was 61.9 months and the median time between diagnosis and surgery was 9.7 months. Three patients presented with metastases, 2 with local recurrence, and 1 patient died of cancer. No contralateral or lymph node recurrence was discovered.ConclusionThis treatment sequence, the feasibility of which was shown in this study, is an alternative for patients who want an IBR to avoid the time spent without one breast. This practice requires upstream multidisciplinary cooperation for optimal patient screening.     

蒽环类为主序贯紫杉类新辅助化疗方案治疗三阴乳腺癌的临床观察

目的 探讨蒽环类为主序贯紫杉醇新辅助化疗方案治疗三阴乳腺癌的临床疗效和安全性.方法 将200例三阴乳腺癌患者按照化疗方案的差异分为观察组112例和对照组88例.对照组患者接受4个周期的CTF(环磷酰胺+阿霉素或表阿霉素+5-氟尿嘧啶)新辅助化疗方案,观察组在4个周期CTF化疗方案后序贯4个周期的紫杉醇,135mg/m2静脉滴注,滴注时间超过3h,用药之前使用抗过敏药物,21 d为1个周期.2组患者分别于化疗结束后2周进行改良乳腺癌根治术.观察比较2组的疗效.结果 观察组有效率(68.8％)显著高于对照组(52.3％)(P＜0.05),部分缓解率、稳定率和进展率无统计学差异(P＞0.05).2组患者不良反应的发生率均较高,但差异无统计学意义(P＞0.05).观察组肿瘤的转移率显著低于对照组(P＜0.05);复发率和死亡率与对照组比较,差异无统计学意义.观察组5年生存率为82.1％,对照组5年生存率为75.0％,差异有统计学意义(P=0.028).结论 蒽环类为主序贯紫杉醇新辅助化疗方案治疗三阴乳腺癌能明显提高患者的有效率和5年生存率,且不增加患者的不良反应,值得临床推广使用.     

Response to Neoadjuvant Chemotherapy in Patients with Advanced Breast Cancer: A Local Hospital Experience

A large proportion of women present with advanced breast cancer in the developing countries with limitedresources. Many of these patients have ulcerated, bleeding lesions or visually obvious masses in the breast.Neoadjuvant chemotherapy is well established as the standard of care and initial management of choice forthese patients. Tumor shrinkage achieved with neoadjuvant chemotherapy has the advantage of converting aninoperable disease to an operable condition, with the option of breast conservation surgery where mastectomyis the only initial option for loco-regional control. Neoadjuvant chemotherapy also provides the earliest possibletreatment of micrometastases and thus improves survival. In the present study, 165 advanced breast cancerfemale patients registered at the Institute of Nuclear Medicine and Oncology, Lahore, Pakistan, between 1st July2005 and 30th June 2007 were evaluated for response to neoadjuvant chemotherapy. Tumor measurements weremade and recorded prior to the first cycle of chemotherapy and 3 weeks after the third cycle. A clinical completeresponse was seen in 7.3%, a partial response in 60%, stable disease in 24% and progressive disease in 9%. Acomplete pathological response was only seen in 3.6% of evaluable patients. We conclude that breast cancer inpatients presenting for neoadjuvant chemotherapy at our facility is more aggressive, generally presents as moreadvanced and bulky local disease, affects a younger population and features a low and unpredictable responseto neoadjuvant chemotherapy.     

局部晚期乳腺癌新辅助放疗研究进展

乳腺癌发病率居世界女性癌症发病率首位,随着医学技术的进步,乳腺癌患者总生存率得到了提高,但是局部晚期乳腺癌的治疗仍然是棘手的临床问题。对于局部晚期乳腺癌,术后辅助放疗是常规治疗手段,而新辅助放疗在局部晚期乳腺癌治疗中地位尚不明确,本文综述局部晚期乳腺癌新辅助放疗的相关研究进展,希望为局部晚期乳腺癌的治疗提供参考。     

Neoadjuvant Chemotherapy in Triple Negative Breast Cancer: Correlation between Androgen Receptor Expression and Pathological Response

Background: There is growing evidence that the response to chemotherapy may be affected by Androgen Receptor (AR) expression suggesting that triple-negative breast cancers (TNBC) AR+ and quadruple negative breast cancer (QNBC) subtypes may have different diseases behavior. Methodology: We retrospectively estimated the predictive value of the AR expression in stage II and stage III TNBC patients treated with neoadjuvant chemotherapy (NAC) and correlated with the rate of pathological response (pCR). Results: Of 89 TNBC patients, 29 patients (32.6%) were TNBC AR+ and 60 patients (67.4) were QNBC. Most of the patients were less than 60 years old. Of note, approximately 62% in the QNBC group were less than 40 years old compared with 39 % in the TNBC AR+ group. The Ki-67 expression was higher in the QNBC in comparison with TNBC AR+ being 86.7% and 65.5%, respectively. QNBC subgroup showed higher rates of pCR compared with TNBC; 60% and 24%, respectively. Higher Ki-67 expression, higher grade, and lymph node involvement were statistically significantly correlated with the rate of pCR in the QNBC group (p=0.02, p=0.04, and p=0.03, respectively). In contrast, no significant association was observed between pCR and clinical-pathological features in the TNBC AR+ group. Conclusion: Our results suggested that the AR expression in TNBC may be applied as a predictive marker for NAC. TNBC AR+ had a lower rate of pCR compared with QNBC, suggesting that this subtype may have a partial chemoresistance.     

Retrospective Analysis of Neoadjuvant Chemotherapy for Breast Cancer in Turkish Patients

Background: Neoadjuvant systemic chemotherapy is the accepted approach for women with locally advancedbreast cancer. Anthracycline- and taxane-based regimens have been extensively studied in clinical trials andconsequently are widely used. In this study aimed to research the complete response (pCR) rates in differentregimens for neoadjuvant setting and determine associated clinical and biological factors. Methods: This studyincluded 63 patients diagnosed with breast carcinoma among 95 patients that had been treated with neoadjuvantchemotherapy between 2007 and 2010. TNM staging system was used for staging. The histologic response toneoadjuvant chemotherapy was characterized as a pCR when there was no evidence of residual invasive tumorin the breast or axillary lymph nodes. Biologic subclassification using estrogen receptor (ER), progesteronereceptor (PR), HER2 were performed. Luminal A was defined as ER+, PR+, HER2-; Luminal B tumor wasdefined as ER+, PR-, HER2-; ER+, PR-, HER2+; ER-, PR+, HER2-; ER+, PR+, HER2+; HER2 like tumorER-, PR+, HER2+; and triple negative tumor ER, PR, HER2 negative. Results: Patients median age was 54.14(min-max: 30-75). Thirty-two patients (50.8%) were premenapousal and 31 (49.2%) were postmenapousal.Staging was performed postoperatively based on the pathology report and appropriated imaging modalitiesThe TNM (tumor, lymph node, metastasis) system was used for clinical and pathological staging. Fifty-seven(90.5%) were invasive ductal carcinomas, 6 (9.5%) were other subtypes. Thirty nine (61.9%) were grade IIand 24 (38.1%) were grade III. Seven (11.1%) patients were stage II and 56 (88.9) patients were stage III. Thepatients were classified for ER, PR receptor and HER2 positivity. Seventeen patients had complete response tochemotherapy. Forty patients (63.5%) were treated with dose dense regimen (cyclophosphamide 600 mg/m2 anddoxorubicine 60 mg/m every two weeks than paclitaxel 175 mg/m2 every two weeks with filgrastim support) 40patients (48%) were treated anthracycline and taxane containing regimens. Thirteen patients (76%) from 17patients with pCR were treated with the dose dense regimen but without statistical significance (p=0.06). pCRwas higher in HER2(-), ER(-), grade III, premenopausal patients. Conclusion: pCR rate was higher in the groupthat treated with dose dense regimen, which should thus be the selected regimen in neoadjuvant setting. Someother factors can predict pCR in Turkish patients, like grade, menopausal status, triple negativity, percentageof ER positivity, and HER2 expression.     

不同新辅助化疗方案治疗乳腺癌的临床观察

目的:比较3组不同新辅助化疗方案治疗乳腺癌的疗效及不良反应.方法:Ⅱ、Ⅲ期乳腺癌68例随机分为3组,A组(FEC)24例、B组(ET)24例、C组(NE)20例,3组临床资料有可比性,分别用FEC、ET或NE化疗方案治疗,3～4周为一个周期.所有患者完成2周期新辅助化疗后评价疗效.结果:乳腺癌原发肿瘤的总有效率(RR)A组为50%(12/24),B组RR为79.2%(19/24,与A组比较P＜0.05),C组RR为75.0%(15/20,与A组比较P＜0.05).C组2例(10.0%)病理完全缓解(pCR),3组无进展病例,Ⅱ期疗效高于Ⅲ期.新辅助化疗前68例患侧腋窝均可触及肿大淋巴结,化疗2周期后A组、B组、C组分别有50.0%(12/24)、66.7%(16/24,与A组比较P＜0.05)、60.0%(12/20,与A组比较P＜0.05)腋窝未触及肿大淋巴结.主要不良反应白细胞下降、胃肠道反应3组相似,ET组脱发程度严重,并伴有关节肌肉疼痛.NE组不良反应以神经毒性和血管静脉炎较突出.结论:3组新辅助化疗方案对乳腺癌的原发肿瘤及腋窝淋巴结转移灶均有效,不良反应均可耐受.B组及C组疗效及不良反应均高于A组.     

Assessing the Impact of Neoadjuvant Chemotherapy on the Management of the Breast and Axilla in Breast Cancer

BackgroundNodal status is a sensitive prognostic indicator in breast cancer. Axillary metastases may be an indication for neoadjuvant systemic therapy. The aims of this study were to compare pathologic response rates to neoadjuvant chemotherapy (NAC) in the breast and axilla across different molecular subtypes of breast cancer and to compare the predictive value of axillary assessment before and after chemotherapy in determining final nodal status in this cohort of patients.Patients and MethodsThe cohort comprised patients undergoing NAC from 2003 to November 2012. Data regarding patient and tumor characteristics, management, and outcomes were obtained from a prospectively maintained database and analyzed using PASW Statistics, version 18 (SPSS Inc, Chicago, IL).ResultsTwo hundred two cancers were identified in 196 patients. One hundred thirty-one (65%) diagnostic axillary procedures were performed, 105 (80%) before NAC, of which 93 (89%) were positive. In 28 (30%), downstaging was noted before NAC. Human epidermal growth factor receptor 2 (HER2) subtypes had the highest rate of complete pathologic response (n = 11 [61%]) and negative axillary clearance (AXCn) (n = 11 [69%]). Of 177 AXCns, 68 (38%) were negative before NAC.ConclusionAXCn in patients undergoing NAC remains controversial. HER2 subtypes are less likely to have axillary involvement after NAC and may demand different management.     

功能MRI在乳腺癌新辅助化疗诊疗过程中的应用

随着功能磁共振的发展,其成为评估新辅助化疗疗效、病灶残留范围的首选检查,对于新辅助后的远期预后有潜在预测价值,在新辅助治疗的各个过程中均具有重要意义。全文就功能MRI在乳腺癌新辅助治疗中的应用进行综述。     

The Neutrophil to Lymphocyte Ratio Predicts the Response to Neoadjuvant Chemotherapy in Luminal B Breast Cancer

Objective: Tumor response to neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients is a predictor foroverall survival. The aim of our study was to determine a relationship between the neutrophil to lymphocyte ratio(NLR) prior to NAC, BC subtypes and the probability of a pathologic complete response (pCR). Materials andMethods: Medical records were collected retrospectively from Centro de Cancer at Red Salud UC-Christus. Clinicaldata collected included peripheral blood cell counts, BC subtype at diagnosis and the pathology report of surgeryafter chemotherapy. Results: A total of 88 patients were analyzed. Approximately, a 25% had a pCR, and displayed asignificant correlation between BC subtype and pCR (p= 0.0138 Chi2); this was more frequent in epidermal growthfactor receptor type 2 (HER2) enriched subtype patients (54%). Luminal B BC patients with a pCR had significantlylower NLR levels (t test, p= 0.0181). Conclusions: HER2-enriched tumors had a higher probability of pCR. In LuminalB tumors, NLR had a statistically significant relationship with the probability of pCR. In this subtype, NLR could bea useful biomarker to predict tumor response to NAC. Further studies including other clinical parameters for systemicinflammation such as platelet counts, intratumoral NLR or body mass index could help identify patients that wouldget the most benefit from NAC.     

铜绿假单胞菌注射液联合新辅助化疗治疗乳腺癌的临床研究*

目的:拟评价铜绿假单胞菌注射液（PA-MSHA 菌苗）联合新辅助化疗治疗乳腺癌的有效性和安全性。方法:本研究为开放、随机、对照试验。试验组乳腺癌患者20例,对照组20例,两组采用相同的化疗方案,试验组加用铜绿假单胞菌注射液。治疗结束后评价疗效,记录患者治疗前、后的Karnofsky 评分,并在治疗前、后抽取患者静脉血,采用双抗体夹心ELISA 法检测患者的免疫功能指标（IFN-γ 、IL- 2、IL- 4、IL- 10）和其他指标（Caspase- 3、VEGF、MMP-2、MMP-9）的变化情况,观察并记录不良反应。结果:治疗后试验组的总缓解率（RR）高于对照组（P<0.05）,试验组的术后病理完全缓解率（pCR ）高于对照组,但差异无统计学意义（P>0.05）;试验组治疗前和治疗后Karnofsky 评分比较,差异有统计学意义（P<0.01）,试验组治疗后Karnofsky 评分显著高于对照组治疗后（P<0.01）;试验组治疗后血清IFN-γ 和IL- 2 水平高于对照组（P<0.01）,IL- 4 和IL- 10水平低于对照组（P<0.05）;试验组治疗后血清Caspase- 3 浓度升高,VEGF、MMP-2 和MMP-9 血清浓度降低,治疗前、后比较差异有统计学意义（P<0.05）;对照组MMP-9 与治疗前相比显著降低（P<0.01）。 结论:铜绿假单胞菌注射液与化疗药物联合应用治疗乳腺癌可以提高总缓解率,能明显改善乳腺癌患者的细胞免疫功能,同时诱导乳腺癌细胞凋亡,降低乳腺癌细胞的侵袭能力,是乳腺癌患者理想的辅助治疗药物。