Phase II open-label study of bevacizumab combined with neoadjuvant anthracycline and taxane therapy for locally advanced breast cancer

BackgroundNeoadjuvant anthracycline- and taxane-based chemotherapy is frequently administered in breast cancer. Pathological complete response (pCR) rates vary according to clinical disease stage and biology of breast cancer. The critical role of angiogenesis in the progression of breast cancer, together with significantly improved efficacy when bevacizumab is combined with chemotherapy in the metastatic setting, provides a strong rationale for evaluating the integration of bevacizumab into neoadjuvant chemotherapy regimens.MethodsA single-arm, multicentre, phase II, open-label study evaluated four 3-weekly cycles of FEC (5-fluorouracil 600 mg/m², epirubicin 90 mg/m² and cyclophosphamide 600 mg/m²) followed by 12 cycles of weekly paclitaxel (80 mg/m²) in combination with bevacizumab 10 mg/kg every 2 weeks as neoadjuvant therapy for HER2-negative stage III locally advanced or inflammatory breast carcinoma. The primary endpoint was pCR rate.ResultsPlanned treatment was completed in 49 of the 56 enrolled patients. In the intent-to-treat population, the pCR rate was 21% and the clinical response rate was 59%. Breast-conserving surgery was achieved in 34% of patients. In the subgroup of 15 patients with triple-negative disease, the pCR rate was 47%. Grade 3 adverse events in ≥5% of patients were neutropenia, leucopenia, asthenia, and rash. One case each of hypertensive retinopathy and post-operative wound complication, both after treatment completion, were considered probably related to bevacizumab. There were no treatment-related deaths and no cardiac function abnormalities.ConclusionsThis study indicates that FEC followed by weekly paclitaxel with bevacizumab is an active neoadjuvant regimen for locally advanced breast cancer, with no major safety concerns.Clinical trial registrationNCT00559845.     

Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change in practice

ObjectivesChemotherapy in the neo adjuvant setting has allowed downsizing of breast tumours thus allowing patients to benefit from breast conservation surgery. The effect of neoadjuvant chemotherapy (NAC) has also been observed in the axilla but most units are still treating the axilla with axillary lymph node dissection (ALND).Materials and methodsA prospective database of breast cancer patients receiving NAC between 2007 and 2016 at a single breast unit was reviewed. The management of the axilla and outcomes was studied.Results165 patients received NAC, 123 (74.5%) were clinically/radiologically node positive and 42 were negative. Median age was 50 years. 26.7% had triple negative disease and 34.5% were HER2 positive. 56/123 (45.5%) patients with positive nodes at the outset responded completely to NAC. 40 patients with positive nodes pre-NAC had post NAC SLNB with 37 requiring adjuvant radiotherapy only. 83/123 went directly to ALND post NAC and of these 27 were node negative and therefore may be considered to have had an unnecessary ALND. Overall mortality was 20.6% (34), local recurrence in the breast or mastectomy scar was 3.6% (6) but there was no recurrence in the axilla (0/165) with a median follow up of 67 months.ConclusionThere is no clear evidence for management of the axilla post NAC. We have used best available evidence to change our practice over the years and our results should encourage others to de-escalate treatment of the axilla in line with the recently published multidisciplinary guidance on axillary surgery following neoadjuvant chemotherapy.     

Axillary Staging in the Neoadjuvant Setting

Neoadjuvant chemotherapy (NAC) is increasingly being used in the treatment of locally advanced breast cancer as well as for early breast cancer. Axillary lymph node dissection has been the standard method of staging the axilla in the neoadjuvant setting. Since the sentinel lymph node biopsy was introduced in the early 1990s, less invasive approaches to axillary staging in patients undergoing neoadjuvant therapy have been proposed. In this review, we discuss the effects of NAC, the imaging modalities that have been used to evaluate the axillary lymph nodes, and the role and timing of sentinel lymph node biopsy in the neoadjuvant setting. Finally, we propose a treatment algorithm for patients undergoing NAC on the basis of the current data.     

剂量密集型蒽环序贯紫杉醇脂质体与蒽环序贯多西紫杉醇在局部晚期HER-2阴性乳腺癌新辅助化疗中的疗效及安全性比较

摘   要 背景与目的：剂量密集型的新辅助化疗在局部晚期乳腺癌中使用越来越广泛。但在剂量密集型的新辅助化疗方案中,使用紫杉醇脂质体的研究较少。本研究探讨剂量密集型蒽环序贯紫杉醇脂质体对比蒽环序贯多西紫杉醇在局部晚期HER-2阴性乳腺癌新辅助化疗中的安全性和疗效。 方法：回顾性分析2017年1月—2018年12月可手术的局部晚期HER-2阴性的女性乳腺癌患者资料。该研究人群均行8周期新辅助化疗,其中196例采用蒽环序贯多西紫杉醇方案（多西紫杉醇组）,48例采用剂量密集型蒽环序贯紫杉醇脂质体方案（紫杉醇脂质体组）。采用倾向性评分匹配（PSM）方法,按照1:1匹配两组基线特征差异后,比较两组患者病理完全缓解（pCR）与临床疗效情况以及不良事件发生率。 结果：通过1:1 PSM匹配后,两组各48例患者。两组间pCR率无统计学意义（22.9% vs. 18.8%,P>0.05）;多西紫杉醇组客观缓解率（ORR）93.7%、疾病控制率（DCR）100.0%,紫杉醇脂质体组ORR与DCR均为100.0%,组间差异无统计学意义（P>0.05）。多西紫杉醇组III~IV度白细胞及中性粒细胞减少症的发生率以及III~IV度恶心、呕吐、乏力和口腔黏膜炎发生率均高于紫杉醇脂质体化疗组（均P<0.05）,两组其他毒副反应的发生率比较,均无统计学意义（均P>0.05）。 结论：在局部晚期HER-2阴性乳腺癌新辅助化疗中,蒽环序贯多西紫杉醇与剂量密集型蒽环序贯紫杉醇脂质体的疗效相当。紫杉醇脂质体化疗组毒副反应明显优于多西紫杉醇化疗组。紫杉醇脂质体可作为HER-2阴性乳腺癌新辅助化疗方案中紫杉醇类药物的优选。     

The predictive value of sentinel lymph node biopsy in locally advanced breast cancer patients who have undergone neoadjuvant chemotherapy

With the increasing usage of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC), there is the need to investigate the routine axillary node dissections performed in this group of patients. Controversy exists about the utility of sentinel node biopsy (SNB), either before or after NAC. With the addition of trastuzumab in the treatment of Her2/neu-positive LABC patients, the validity of SNB in this subset population needs to be investigated. A retrospective study of 20 patients who underwent NAC for LABC was undertaken. The pathology of the axillary nodes, sentinel nodes, and primary tumor after neoadjuvant chemotherapy were examined. Twenty patients underwent NAC with doxorubicin and cyclophosphamide, followed sequentially by paclitaxel and carboplatin, with or without trastuzumab based on Her2/neu status. Post chemotherapy, 20 patients underwent mastectomy or lumpectomy with SNB with axillary node dissections. The overall accuracy of SNB was 95 per cent with a false-negative rate of 14 per cent (1/7). In Her2/neu-positive patients, overall accuracy was 100 per cent (8/8) and a false-negative rate of zero per cent. Sentinel node biopsy is a viable option in patients who have undergone NAC. Her2/neu-positive patients who had undergone NAC with trastuzumab had comparable accuracy for sentinel node biopsy in predicting axillary node status.     

FDG PET/CT during neoadjuvant chemotherapy may predict response in ER-positive/HER2-negative and triple negative,but not in HER2-positive breast cancer

BackgroundResponse monitoring with MRI during neoadjuvant chemotherapy (NAC) in breast cancer is promising, but knowledge of breast cancer subtype is essential. The aim of the present study was to evaluate the relevance of breast cancer subtypes for monitoring of therapy response during NAC with 18F-FDG PET/CT.MethodsEvaluation included 98 women with stages II and III breast cancer. PET/CTs were performed before and after six or eight weeks of NAC. FDG uptake was quantified using maximum standardized uptake values (SUVmax). Tumors were divided into three subtypes: HER2-positive, ER-positive/HER2-negative, and triple negative. Tumor response at surgery was assessed dichotomously (presence or absence of residual disease) and ordinally (breast response index, representing relative change in tumor stage). Multivariate regression and receiver operating characteristic (ROC) analyses were employed to determine associations with pathological response.ResultsA (near) complete pathological response was seen in 19 (76%) of 25 HER2-positive, 7 (16%) of 45 ER-positive/HER2-negative, and 20 (71%) of 28 triple negative tumors. Multivariate regression of pathological response indicated a significant interaction between change in FDG uptake and breast cancer subtype. The area under the ROC curve was 0.35 (0.12–0.64) for HER2-positive, 0.90 (0.76–1.00) for ER-positive/HER2-negative, and 0.96 (0.86–1.00) for triple negative tumors. We found no association between age, stage, histology, or baseline SUVmax and pathological response.ConclusionResponse monitoring with PET/CT during NAC in breast cancer seems feasible, but is dependent on the breast cancer subtype. PET/CT may predict response in ER-positive/HER2-negative and triple negative tumors, but seems less accurate in HER2-positive tumors.     

乳腺癌新辅助化疗后原发灶临床完全缓解对腋淋巴结转阴的预测作用

目的 判断腋窝淋巴结阳性乳腺癌新辅助化疗(neoadjuvant chemotherapy,NAC)后原发灶临床完全缓解能否预测腋窝淋巴结病理转阴.方法 2016年10月 ～2019年10月收治的乳腺癌病人95例,淋巴结穿刺均阳性,临床分期T1-3,N1-2期,且均完成NAC后有腋窝淋巴结清扫(axillary lym...     

Sentinel lymph node biopsy before versus after neoadjuvant chemotherapy for breast cancer

Axillary lymph node status is the most important prognostic factor in the treatment of breast cancer. In recent years, sentinel lymph node biopsy (SLNB) has replaced conventional axillary lymph node dissection for predicting axillary lymph node status with higher accuracy. Moreover, neoadjuvant chemotherapy (NAC) is being used increasingly to treat not only patients with locally advanced inoperative breast cancer, but also those with initially operable breast cancer. The application of SLNB has now expanded to include this patient population, who were not previously considered good candidates for SLNB. A number of recent studies have evaluated the feasibility and accuracy of SLNB after NAC in breast cancer patients. Moreover, SLNB has been shown to be accurate in patients scheduled to receive NAC, and repeat SLNB has been performed after NAC for patients with positive nodes detected by the initial SLNB before NAC. Thus, the optimal timing of SLNB for patients with breast cancer in the neoadjuvant setting remains controversial. This article reviews the issues surrounding SLNB before vs. after NAC, according to the published literature and our experience.     

新辅助治疗对雌激素受体低表达/人类表皮生长因子受体2阳性乳腺癌腋窝淋巴结状态的影响

目的评估人类表皮生长因子受体2（HER2）阳性乳腺癌患者接受不同新辅助治疗（NAC）方案后腋窝淋巴结病理缓解情况及影响因素。 方法纳入2010年11月至2015年12月中山市人民医院收治的100例HER2阳性、Ⅱa~Ⅲc期乳腺癌患者，在NAC前通过触诊和细针穿刺（FNA）评估腋窝淋巴结状态。所有患者接受4~6个周期的PCrb（紫杉醇175 mg/m²和卡铂AUC=6，每3周），部分患者接受联合曲妥珠单抗（6 mg/kg每3周，首剂8 mg/kg）。 结果62例通过FNA确定为腋窝淋巴结阳性（A组），38例通过FNA或触诊确定为腋窝淋巴结阴性（B组）。其中A组总体腋窝淋巴结病理阴性率（pNNR）为53.2％，B组为71.1％。雌激素受体（ER）低表达/HER2阳性患者的pNNR最高，A组为81.0％，B组86.7％。多因素分析显示，联合曲妥珠单抗和ER状态是预测HER2阳性乳腺癌pNNR的独立因素。 结论对于治疗前腋窝淋巴结阳性的乳腺癌患者，如果NAC联合靶向治疗后前哨淋巴结阴性，ER低表达/HER2阳性就不需要腋窝淋巴结清扫。     

Incidence and Impact of Documented Eradication of Breast Cancer Axillary Lymph Node Metastases Before Surgery in Patients Treated With Neoadjuvant Chemotherapy

OBJECTIVE: To determine the incidence and prognostic significance of documented eradication of breast cancer axillary lymph node (ALN) metastases after neoadjuvant chemotherapy. SUMMARY BACKGROUND DATA: Neoadjuvant chemotherapy is the standard of care for patients with locally advanced breast cancer and is being evaluated in patients with earlier-stage operable disease. METHODS: One hundred ninety-one patients with locally advanced breast cancer and cytologically documented ALN metastases were treated in two prospective trials of doxorubicin-based neoadjuvant chemotherapy. Patients had breast surgery with level I and II axillary dissection followed by additional chemotherapy and radiation treatment. Nodal sections from 43 patients who were originally identified as having negative ALNs at surgery were reevaluated and histologically confirmed to be without metastases. An additional 1112 sections from these lymph node blocks were obtained; half were stained with an anticytokeratin antibody cocktail and analyzed. Survival was calculated using the Kaplan-Meier method. RESULTS: Of 191 patients with positive ALNs at diagnosis, 23% (43 patients) were converted to a negative axillary nodal status on histologic examination (median number of nodes removed = 16). Of the 43 patients with complete axillary conversion, 26% (n = 11) had N1 disease and 74% (n = 32) had N2 disease. On univariate analysis, patients with complete versus incomplete histologic axillary conversion were more likely to have initial estrogen-receptor-negative tumors, smaller primary tumors, and a complete pathologic response in the primary tumor. The 5-year disease-free survival rates were 87% in patients with preoperative eradication of axillary metastases and 51% for patients with residual nodal disease after neoadjuvant chemotherapy. Of the 39 patients with complete histologic conversion for whom nodal blocks were available, occult nodal metastases were found in additional nodal sections in 4 patients (10%). At a median follow-up of 61 months, the 5-year disease-free survival rates were 87% in patients without occult nodal metastases and 75% in patients with occult nodal metastases. CONCLUSIONS: Neoadjuvant chemotherapy can completely clear the axilla of microscopic disease before surgery, and occult metastases are found in only 10% of patients with a histologically negative axilla. The results of this study have implications for the potential use of sentinel lymph node biopsy as an alternative to axillary dissection in patients treated with neoadjuvant chemotherapy.     

Surgical Axillary Staging Before Neoadjuvant Chemotherapy: Who Gets It and Why We Should Avoid It

Background

Surgical axillary staging demonstrating positive nodal disease before neoadjuvant chemotherapy (NAC) necessitates axillary lymph node dissection (ALND) post-NAC. Despite evidence supporting post-NAC surgical staging, we hypothesized that there is persistent use of pre-NAC staging and that it is associated with aggressive clinicopathologic features and a higher rate of subsequent ALND.

Patients and Methods

Stage I–III breast cancer patients who underwent lymph node staging surgery and received NAC between 2013 and 2017 in the National Cancer Database were included. Sequence of staging surgery and chemotherapy administration was determined. Multivariable regression was used to assess characteristics associated with pre-NAC staging. Rate of ALND was compared between those who had pre- and post-NAC surgical axillary staging.

Results

In total, 120,538 met inclusion; 68% received NAC first and 32% had pre-NAC staging. Pre-NAC staging surgery was associated with younger age (age < 30 versus 40–49 years, HR 1.1) and decreased with older age (ages 70–79/80+ versus 40–49 years, HR 0.86 and 0.73). Advancing clinical T stage, lobular subtype, higher grade, and HR+/HER2? subtype were also associated with pre-NAC surgical staging. Women who underwent pre-NAC surgical staging were more likely to undergo ALND.

Conclusions

Over 30% of women underwent surgical axillary staging prior to NAC, resulting in higher rates of ALND in this cohort. While certain features suggestive of aggressive behavior (grade and T stage) were associated with pre-NAC surgical axillary staging, women with more aggressive tumor subtypes (triple negative/HER2+) were less likely to undergo pre-NAC surgical axillary staging. Pre-NAC surgical axillary staging should be performed only in rare circumstances to avoid unnecessary ALND.

     

Pathological complete response of locally advanced gastric cancer after four courses of neoadjuvant chemotherapy with paclitaxel plus cisplatin: report of a case

We report a case of advanced gastric carcinoma treated successfully by four courses of neoadjuvant chemotherapy (NAC) with paclitaxel and cisplatin. The patient was a 43-year-old man with advanced gastric cancer, clinically diagnosed as P0H0M0CY0T3N2, which had invaded the upper body of the stomach and esophagus. He was entered into a clinical trial and received the following NAC regimen: paclitaxel 80 mg/m², and cisplatin 25 mg/m², on days 1, 8, and 15, followed by a rest on day 22, as one course. The lymph nodes had reduced in size to 59% after two courses and to 40% after four courses, with no sign of severe toxicity. Subsequently, he underwent D2 total gastrectomy with pancreatico-splenectomy. On microscopic examinations, no tumor cells were detected in the ulcer scar of the resected stomach or the regional lymph nodes. Thus, we discuss the potential of long-term NAC, especially for responders to two initial courses.     

Time to initiation of neo‐adjuvant chemotherapy for breast cancer treatment does not influence patient survival: A study of US breast cancer patients

Delays in the initiation of adjuvant chemotherapy or radiation therapy are associated with worse outcomes in patients undergoing treatment for breast cancer. However, the impact of the time to initiation of neo‐adjuvant chemotherapy (NAC) on patient outcomes has not previously been studied. The purpose of this study was to determine whether delays in NAC initiation impact patient survival. The National Cancer Database was queried for women ≥ 18 years old who underwent NAC within 6 months of being diagnosed with stage I‐III invasive breast cancer in 2010‐2011. ER+ or PR+, Her2? cancers were excluded from analysis. Multivariable Cox proportional hazard modeling was used to evaluate the relationship between time to NAC, sociodemographic, diagnosis, and treatment factors with patient survival. The median age of the 12 806 women included in this study was 52 (range 21‐90) with 62% presenting with cT2 disease and 62% with nodal involvement. Half of the women (50%) had triple negative, 30% ER/PR+Her2+ and 20% ER?PR?Her2+ cancers. The median time to starting NAC was 4 weeks (range 0‐26) for all subtypes. Time to NAC initiation was not associated with a difference in survival for triple negative or Her2+ cancers. Delays from diagnosis to starting NAC are not associated with worse survival for patients with Her2+ or triple negative breast cancer. This study demonstrates that the majority of women in the modern era start NAC in a timely fashion and delays in starting NAC within 6 months of diagnosis do not impact long‐term patient outcomes.     

Correlation Between Clinical Nodal Status and Sentinel Lymph Node Biopsy False Negative Rate After Neoadjuvant Chemotherapy

Background

Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. It is now being used to treat operable breast cancer to facilitate breast-conserving surgery, but the accuracy of sentinel lymph node biopsy (SLNB) in breast cancer patients receiving NAC remains open to considerable debate.

Methods

We enrolled 96 patients with stage II–III breast cancer who received NAC from January 2001 to July 2010. All patients underwent breast surgery and SLNB, followed immediately by complete axillary lymph node dissection (ALND). Sentinel lymph nodes were detected with blue dye and radiocolloid injected intradermally just above the tumor and then evaluated with hematoxylin and eosin and immunohistochemical staining.

Results

The overall identification rate for SLNB was 87.5?% (84/96); the false negative rate (FNR) was 24.5?% (12/49); and the accuracy rate was 85.7?% (72/84). The FNR was significantly lower in clinically node-negative patients than in node-positive patients before NAC (5.5?% vs. 35.5?%; p?=?0.001). Accuracy was also significantly higher in clinically node-negative patients than in node-positive patients before NAC (97.2?% vs. 77.1?%; p?=?0.009). The FNR was 27.3?% among 46 clinically node-positive patients before NAC who were clinically node-negative after NAC. Among 12 patients with a complete tumor response (CR), the FNR was 0?%, compared with 26.1?% for 83 patients with a partial response and stable disease (p?=?0.404).

Conclusions

Although associated with a high FNR after NAC, SLNB would have successfully replaced ALND in clinically node-negative patients before NAC and in patients with a CR after NAC.     

Breast cancer during pregnancy and lactation

Breast cancer is the most frequently seen cancer in pregnancy and lactation, but the incidence is low, the disease being seen in approximately 0.03% of pregnancies. Only 1% to 2% of breast cancer overall is diagnosed during pregnancy or lactation. There is no evidence to implicate pregnancy or lactation in either the etiology or the progression of breast cancer. Careful breast examination early in the pregnancy is very important to find solid masses that require biopsy before breast engorgement hides them. Therapeutic options vary, depending on the stage of disease and the stage of the pregnancy. Operable disease in the first 6 to 7 months of the pregnancy should be treated by mastectomy, as irradiation is contraindicated. Late in the pregnancy, a lumpectomy and axillary dissection can be done, with irradiation being delayed until after delivery. General anesthesia is safe if the usual precautions are taken to compensate for the physiologic changes induced by pregnancy. Unfortunately, delay in diagnosis is common, and 70% to 89% of patients with operable primary lesions have positive axillary lymph nodes. Late stage appears to be the only reason for the generally worse prognosis in these patients, as stage for stage, they have a course similar to that of nonpregnant patients. Adjuvant chemotherapy can be considered late in the pregnancy but should usually be delayed until after delivery. In patients with locally advanced or metastatic cancer diagnosed early in the pregnancy, for whom both chemotherapy and radiation therapy would normally be recommended, consideration must be given to termination of the pregnancy. There is no evidence that termination of pregnancy improves the outlook for the patients, but it does permit standard aggressive therapy in advanced disease.     

An ovarian mass after breast cancer: Metachronous carcinoma or metastasis? A case report

IntroductionDifferentiating between primary and secondary ovarian cancer can be a difficult task. In hereditary conditions breast malignancies and primary ovarian cancer often coexist.Presentation of caseWe present a 45-year-old patient with an ovarian mass two years after the diagnosis of a lobular, triple negative breast carcinoma. There was concern whether the lesion represented a metachronous ovarian cancer or a metastasis of the lobular carcinoma. The final histological examination showed a metastatic lesion, deriving from the lobular breast carcinoma, as evidenced by the immunohistochemical profile; nevertheless, there were changes in hormonal receptor expression in the metastatic lesion compared to the primary, triple negative tumor. The patient underwent genetic testing for BRCA1 and BRCA2 mutations and was negative. In the adjuvant setting the patient received 6 cycles of chemotherapy with carboplatin and paclitaxel; eighteen months later, the patient remains without disease recurrence.Discussion and conclusionThis case report highlights the role of imaging, histology and predominantly immunohistochemistry as valuable tools in the assessment of ambiguous ovarian lesions after breast cancer.     

Strategies for Improving the Clinical Benefit of Antiangiogenic Drug Based Therapies for Breast Cancer

Viewed as a whole, the aggregate outcomes of a number of positive randomized phase III clinical trial results evaluating the VEGF-pathway targeting antiangiogenic drug bevacizumab, with or without concurrent chemotherapy, in metastatic breast cancer patients have been disappointingly modest. In the case of antiangiogenic tyrosine kinase inhibitors (TKIs) the results have been negative. Nevertheless, several findings indicate antiangiogenic drugs, especially bevacizumab, are active and can lead to demonstrable clinical benefit in some patients, thus stimulating research into developing strategies to significantly improve their efficacy and reduce toxicity. Some of these initiatives include: 1) discovery and validation of predictive markers that can prospectively identify patients more likely to benefit from antiangiogenic therapy; 2) recognition that the nature of the chemotherapy partner or backbone can strongly impact outcomes when combined with antiangiogenic drugs such as bevacizumab, and thus developing what may be improved combination chemotherapy partner regimens, e.g. metronomic chemotherapy; 3) evaluating prospectively in more depth whether subtypes of the disease—especially triple negative or inflammatory breast cancer—are more responsive to antiangiogenic therapy than other subtypes; 4) evaluating new agents that inhibit angiogenesis in a VEGF-independent manner and other types of drug that can be effectively combined with antiangiogenics, e.g. c-met inhibitors; 5) uncovering the basis of resistance or relapse/progression on the therapy with antiangiogenic drugs; 6) development of improved predictive preclinical breast cancer models for therapy testing, e.g. treatment of mice with established multi-organ breast cancer metastatic disease or genetically engineered mouse models of breast cancer, or mice bearing patient derived breast cancer tissue xenografts.     

Cisplatin–gemcitabine therapy in metastatic breast cancer: Improved outcome in triple negative breast cancer patients compared to non-triple negative patients

Triple negative or basal-like breast cancers lack expression of estrogen, progesterone and HER2neu receptors. There are no specific treatment guidelines for this group of patients, however, it has been postulated that their phenotypic and molecular similarity to BRCA-1 related cancers would confer sensitivity to certain cytotoxic agents like cisplatin (CDDP). The aim of the study was to retrospectively examine the clinical outcome at our institution of patients with metastatic breast cancer treated with CDDP and gemcitabine combination chemotherapy who had triple negative breast cancer compared to non-triple negative breast cancer. Thirty-six patients with metastatic breast cancer were treated with CDDP and gemcitabine combination chemotherapy, 17 of whom were triple negative (47%) and 19 were non-triple negative (53%). The median progression free survival for triple negative and non-triple negative metastatic breast cancer patients were 5.3 months and 1.7 months respectively (p = 0.058). By multivariate Cox proportional hazard model after adjusting for age, race and menopausal status the risk of progression was reduced by 47% for triple negative compared to non-triple negative metastatic breast cancer patients (HR = 0.53, p = 0.071).ConclusionsOur results suggest an improved outcome for metastatic triple negative breast cancer patients compared to non-triple negative breast cancer patients when treated with cisplatin and gemcitabine combination chemotherapy.     

Variation in use of neoadjuvant chemotherapy in patients with stage III breast cancer: Results of the Dutch national breast cancer audit

ObjectivesNeoadjuvant chemotherapy (NAC) is important in the optimal treatment of patients with locally advanced (stage III) breast cancer (BC). The objective of this study was to examine the clinical practice of NAC for stage III BC patients in all Dutch hospitals participating in BC care.Materials and methodsAll patients aged 18–70 years who received surgery for stage III BC from January 2011 to September 2015 were selected from the national multidisciplinary NABON Breast Cancer Audit. Multivariable logistic regression was used to assess independent predictors of NAC use, focussing on hospital factors.ResultsA total of 1230 out of 1556 patients with stage III BC (79%) received NAC prior to surgery. The use of NAC did not change over time. We observed a large variation of NAC use between hospitals (0–100%). Age <50 years, breast MRI, large tumour size, advanced nodal disease, negative hormone receptor status and hospital participation in neoadjuvant clinical studies were significant independent predictors of NAC use (all P < 0.001). NAC use in stage III BC was not influenced by hospital type and hospital surgical volume. After adjustment for all independent predictors, variation in NAC use between hospitals remained (0% to 97%).ConclusionNAC was used in 79% of patients with stage III BC, which represent a high quality of care in the NL. Patient, tumour, clinical management and hospital factors could not explain considerable variation in its use between hospitals. Hospital participation in neoadjuvant studies did show to improve the use of NAC in daily practice.     

Role of axillary lymph node dissection after tumor downstaging with induction chemotherapy for locally advanced breast cancer

Background: Induction chemotherapy has become the standard of care for patients with locally advanced breast cancer (LABC) and currently is being evaluated in prospective clinical trials in patients with earlier-stage disease. To better gauge the role of axillary lymph node dissection in patients with LABC this study was performed to assess initial axillary status on physical and ultrasound examination, axillary tumor downstaging following induction chemotherapy, and the accuracy of physical examination compared with axillary sonography in predicting which patients will have axillary lymph node metastases found on pathologic examination. Methods: Between 1992 and 1996, 147 consecutive patients with LABC were registered in a prospective trial of induction chemotherapy using 5-fluorouracil, doxorubicin, and cyclophosphamide. Physical and ultrasound examinations of the axilla were performed at diagnosis and after induction chemotherapy. Segmental resection with axillary lymph node dissection or modified radical mastectomy was performed, followed by postoperative chemotherapy and irradiation of the breast or chest wall and regional lymphatics. Results: Following induction chemotherapy, 43 (32%) of the 133 patients with clinically positive lymph nodes on initial examination had axillary tumor downstaging as assessed by physical and ultrasound examination. The sensitivity of axillary sonography in identifying axillary metastases was significantly higher than that of physical examination (62% vs. 45%,P=.012). The specificity of physical examination (84%) was higher than that of sonography (70%), but the difference did not reach statistical significance. Among the 55 patients in whom the findings of both physical and ultrasound examination of the axilla were negative following induction chemotherapy, 29 patients (53%) were found to have axillary lymph node metastases on pathologic examination of the axillary contents. However, 28 (97%) of these patients had either 1 to 3 positive lymph nodes or only micrometastases 2 to 5 mm in diameter. Conclusions: Preoperative clinical assessment of the axilla by physical examination combined with ultrasound examination is not completely accurate in predicting metastases in patients with LABC following tumor downstaging. However, patients with negative findings on both physical and ultrasound examinations of the axilla may be potential candidates for omission of axillary dissection if the axilla will be irradiated because minimal axillary disease remains. Patients who have positive findings on preoperative physical or ultrasound examinations should receive axillary dissection to ensure local control. A prospective randomized trial of axillary dissection versus axillary radiotherapy in patients with a clinically negative axilla following induction chemotherapy is currently underway.Presented at the 51st Annual Cancer Symposium of The Society of Surgical Oncology, San Diego, California, March 28, 1998.