Breast cancer subtypes affect the nodal response after neoadjuvant chemotherapy in locally advanced breast cancer: Are we ready to endorse axillary conservation?

We evaluated the impact of breast cancer subtypes on pathologic complete response (pCR) in 181 patients with positive nodes undergoing neoadjuvant chemotherapy (NAC). After NAC, patients underwent surgery, with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND). In 28.2% of cases a pCR was achieved, with the highest rate in Her2+ and triple negative tumors. Overall, nodal pCR was more frequent than breast pCR (P = 0.003) with higher percentages in Her2+ and LLB‐Her2+ (P < 0.05). In the Her2+ group, nodal pCR was observed only with breast pCR. Thus, in Her2+ tumors, breast pCR predicts node pCR, supporting the use of SLNB in this subgroup to stage the axilla avoiding ALND.     

Evaluating the preoperative breast cancer characteristics affecting the accuracy of axillary ultrasound staging

We evaluate the preoperative breast cancer (BC) characteristics that affect the diagnostic accuracy of axillary ultrasound (US) and determine the reliability of US in the different subgroups of BC patients. Axillary US assessments in women with invasive BC diagnosed between 2009 and 2016 in a single institution were retrospectively reviewed. The diagnostic accuracy of axillary US was obtained using surgical nodal histology as the gold standard. Preoperative breast tumor sonographic and histological factors affecting axillary US diagnostic accuracy were examined. Of the 605 newly diagnosed invasive BC cases reviewed, 251 (41.5%) had nodal metastases. Axillary US sensitivity was 75.7%, specificity 92.9%, positive predictive value 88.4%, negative predictive value 84.4%, and false‐negative rate 24.3%. Lower US sensitivity was seen with invasive lobular cancer (ILC) (P = .043), grade I/II, (P = .021), unifocal (P = .039), and smaller tumors (P < .001). US specificity was lower in grade III (P < .001), estrogen receptor (ER)‐negative (P < .001), progesterone receptor (PR)‐negative (P = .004), HER2‐positive (P = .015), triple‐negative (P = .001), and larger breast tumors (P < .001). US has moderate sensitivity and good specificity in detecting metastatic axillary lymph nodes. Based on preoperative cancer characteristics, US was less sensitive for nodal metastases from ILC, unifocal, lower grade, and smaller breast tumors. It was also less specific in grade III, ER‐negative, PR‐negative, HER2‐positive, triple‐negative, and larger breast tumors. Caution is suggested in interpreting the US axillary findings of patients with these preoperative tumor features.     

Does use of axillary ultrasound in clinically node‐negative patients receiving neo‐adjuvant systemic therapy for breast cancer lead to surgical overtreatment?

Increased use of neo‐adjuvant chemotherapy (NAC) for breast cancer has raised uncertainty regarding staging of the axilla, particularly for patients with a clinically negative axillary physical examination (PE). We sought to determine whether axillary ultrasound (AUS) prior to NAC to identify occult nodal disease is beneficial in patients with a clinically negative examination by evaluating the difference in nodal burden on final pathology in those with abnormal vs normal AUS. A retrospective review of an institutional cancer registry identified patients who underwent NAC for breast cancer and had a pretreatment AUS. Differences in the number of positive lymph nodes (PLN) in patients with a normal axillary PE and abnormal vs normal AUS prior to NAC were determined. A total of 120 patients who received NAC had a negative axillary PE prior to treatment. Fifty‐three had an abnormal AUS and biopsy‐proven lymph node (LN) involvement. In patients with an abnormal AUS, median number of PLNs at surgery was 1 vs 0 for those with a normal AUS (mean difference of 2.12, P < .0001). Of those patients with an abnormal AUS and biopsy‐proven LN involvement, 87% underwent axillary lymph node dissection (ALND) and nearly half had no PLN on final pathology (N = 23, 43%). Patients with a clinically negative axilla and an abnormal AUS were more likely to have PLN at the time of surgery. However, almost half of those patients had no residual LN involvement. Routine AUS prior to NAC may lead to more extensive surgical management of the axilla.     

False‐negative rate of ultrasound‐guided fine‐needle aspiration cytology for identifying axillary lymph node metastasis in breast cancer patients

Axillary nodal status remains an important determinant of prognosis and of the therapeutic strategy in patients with a newly diagnosed breast cancer. The aim of this study was to assess the false‐negative rate of ultrasound (US)‐guided fine‐needle aspiration cytology (FNAC) in axillary node staging at breast cancer diagnosis. All patients with a newly diagnosed breast cancer who had an indeterminate or suspicious axillary node sampled with an FNAC between 2007 and 2014 were included in the study. FNAC results were compared to the final histopathological results of surgically removed axillary lymph nodes. Patient demographics, tumor, and nodal characteristics were analyzed. Diagnostic accuracy tests were performed using IBM SPSS, version 22. A total of 3515 patients with breast cancer were identified, 675 of whom had ultrasound‐guided FNAC of ipsilateral axillary lymph nodes (mean age: 55 years; Range: 26‐84). A benign (C2) result was observed in 52% (n = 351) and a malignant (C5) result in 35% (n = 238). C1 was obtained in 11% (n = 76), C3 in 0.6% (n = 4), and C4 in 0.9% (n = 6). Of the 238 patients with a malignant (C5) FNAC, 99.6% had confirmed axillary lymph node metastatic disease on histopathology. Of the 351 patients with benign FNAC (C2), 31% (n = 108) of patients had a positive lymph node on histology. The false‐negative rate of preoperative FNAC remains too high (31%) to omit definitive surgical staging of the axilla. The high diagnostic accuracy when a positive FNAC is obtained allows appropriate tailored decisions regarding definitive therapy.     

Pre-operative staging of the axilla in primary breast cancer. By redefining the abnormal appearing node can we reduce investigations without affecting overall treatment?

Primary axillary clearance (ANC) is currently performed based on cytology from abnormal appearing node(s) without considering extent of involvement. We assessed correlation between nodal burden and nodal appearance.439 invasive breast cancer cases underwent axillary ultrasound (AUSS) with nodal scoring [UN2-normal (n = 293), UN3-indeterminate (n = 84), UN4-suspicious (n = 29), and UN5-replaced (n = 34)]. Fine needle aspiration cytology (FNAC) of all UN3, UN4 & UN5 nodes was performed.64 cases had nodal metastases identified pre-operatively, proceeding to primary ANC. 375 cases underwent sentinel lymph node biopsy (SLNB), 64 of whom were found to have nodal metastases. Likelihood of metastases and nodal burden was related to AUSS score. >50% of malignant UN4 & UN5 scored nodes had ≥4 metastases compared to 19% of UN3 nodes.Most UN3 nodes are either not involved or have low metastatic burden which may be better served by SLNB alone. Redefining our FNAC nodal threshold could potentially avoid additional ANC morbidity and reduce pre-operative workload.     

Sentinel node biopsy versus low axillary sampling in women with clinically node negative operable breast cancer

BackgroundSentinel node biopsy (SNB) was initially conceived as excision of the first station axillary lymph node(s) (LN) identified by radioactive and/or blue dye uptake. The definition was subsequently enlarged to also include palpable lymph nodes in the vicinity of sentinel node(s) (SN). We reasoned that the excision of this combination of nodes might be best achieved by sampling the lower axilla.MethodsEach patient underwent low axillary sampling (LAS) and identification of SN in the excised specimen followed by complete axillary lymph node dissection (ALND). LAS was defined as excision of all fibrofatty tissue overlying the second digitation of serratus anterior below the intercostobrachial nerve and was carried out following a pre-operative injection of radioactive colloid and an intra-operative injection of blue dye. Blue and/or hot nodes (B&/HN) in the dissected tissue and remaining axilla, along with any palpable nodes within the sampled tissue, were defined as SN. The primary endpoint of the study was to compare false negative rates (FNR) of SN with that of LAS in predicting axillary LN status (NCT00128362).FindingsThe study was performed between March 2004 and December 2011 in 478 women with clinically node negative axilla. On histopathological evaluation the median tumor size was 2.5 cm and axillary nodal metastases were found in 34.1% of patients. The FNR of SNB (12.7%, 95% CI 8.1–19.4) and LAS (10.5%, 95% CI 6.6–16.2) were not significantly different (p = 0.56). The FNR of B&/HN alone, without palpable nodes, (29.0%, 95% CI 22.5–36.6) was significantly inferior to those of SNB (p = 0.0007) and LAS (p = 0.0003).InterpretationLAS is as accurate as SNB in predicting axillary LN status in women with clinically node negative operable breast cancer. Confining SNB procedure to excision of B&/HN, significantly increases the risk of leaving behind metastatic lymph nodes in the axilla. LAS is an effective and low cost procedure that minimizes axillary surgery and can be implemented widely.Registry Name: Clinicaltrials.gov.Registration Number: NCT00128362.     

Predictive factors for omitting lymphadenectomy in patients with node‐positive breast cancer treated with neo‐adjuvant systemic therapy

A pathologic complete response (pCR) in the axilla occurs in 30%‐40% of patients with initially node‐positive breast cancer after neo‐adjuvant chemotherapy (NACT). Debate persists about whether to perform systematic axillary lymphadenectomy (ALND) in patients with initial node‐positive disease and clinical complete response after NACT. We aimed to identify predictive factors of axillary pCR (ypN0) after NACT. This retrospective study analyzed data for all patients with initial biopsy‐proven node‐positive disease who underwent ALND after NACT between June 2008 and December 2016 at our institution. Clinical and pathologic features, recurrence and specific mortality rates were compared between patients who achieved an axillary pCR and those who did not (ypN0 vs ypN+, respectively). A total of 331 patients were included, of whom 128 (38.7%) became ypN0 after NACT. Among patients with >2 suspicious axillary lymph nodes before treatment, 54 (38%) achieved ypN0 status. The independent predictors of ypN0 were Ki‐67 > 30 (OR 1.98; 95% CI, 1.146‐3.381), HER2 positivity (OR 2.6; 95% CI, 1.354‐5.108), nonluminal molecular‐like subtype (OR 4.15; 95% CI, 2.068‐5.108), and clinical complete response, defined as negative clinical and ultrasonographic findings (OR 2.8; 95% CI, 1.110‐7.081). After a mean follow‐up of 61 months, distant disease‐free and overall survival rates were higher in patients with ypN0 disease (HR 4.14; 95% CI, 2.03‐8.43) than ypN+ patients. Complete clinical response and the presence of nonluminal molecular‐like subtypes independently predicted ypN0. Patients meeting these criteria might be suitable form omitting ALND and just performing targeted axillary procedures to patients meeting these criteria.     

The role of axillary reverse mapping in intraoperative nodal palpation during sentinel lymph node biopsy

Intraoperative nodal palpation in the axilla is a mandatory part of sentinel lymph node biopsy. However, there is no consensus regarding the definition of suspicious palpable node. The sampling rate and involvement rate of suspicious palpable nodes are inconsistent. We hypothesized that axillary reverse mapping is helpful to select suspicious palpable sentinel lymph nodes more accurately. Patients with clinically negative nodes underwent sentinel lymph node biopsy with intraoperative nodal palpation and axillary reverse mapping. Blue and hot nodes were removed as sentinel lymph nodes. Suspicious palpable nodes that were neither blue nor hot were removed as palpable sentinel lymph nodes. Nodes around blue and hot sentinel lymph node were incidentally removed as para-sentinel lymph nodes. Fluorescent nodes were considered axillary reverse mapping nodes. Patients with positive sentinel lymph node underwent axillary lymph node dissection. Palpable sentinel lymph nodes and para-sentinel lymph nodes were removed in 130 (15%) of 850 patients with clinically negative nodes. Although palpable sentinel lymph nodes and para-sentinel lymph nodes were involved in 19 (15%) of 130 patients, fluorescent palpable sentinel lymph nodes were involved only in 2 patients and fluorescent para-sentinel lymph nodes were not involved. When excluding fluorescent palpable sentinel lymph nodes and para-sentinel lymph nodes, the sampling rate of suspicious palpable nodes significantly decreased (15% vs. 5%, p < 0.01) and the involvement rate of palpable sentinel lymph nodes significantly increased (15% vs. 31%, p < 0.05). Axillary reverse mapping is helpful to avoid an unnecessary removal of palpable nodes without metastases.     

Clinical Significance of Axillary Microresiduals After Neoadjuvant Chemotherapy in Breast Cancer Patients with Cytologically Proven Metastases

Background  Neoadjuvant chemotherapy (NAC) has been widely accepted for advanced breast cancer patients, and pathological complete remission (pCR) was revealed to be an important prognostic factor. The pCR status of cytologically proven axillary metastases (ALN-pCR) offers a more powerful prognostic predictor than pCR of the main tumor. This study evaluated the clinical significance of residual micrometastases and discusses screening methods after NAC in patients with cytologically proven axillary metastases. Methods  Eighty patients with a diagnosis of cytologically proven axillary metastases received NAC. All dissected lymph nodes were evaluated using multislice sectioning and cytokeratin immunohistochemistry, and categorized into four groups: no metastases (ALN-pCR), and with metastases ≤0.2 mm (ALN-itc), >0.2 mm but ≤2 mm (ALN-mic), and >2 mm (ALN-mac). Disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan–Meier method based on the status of residual metastases. Results  DFS in patients with ALN-pCR and ALN-itc was significantly longer than that with ALN-mic (P = 0.007, P = 0.045, respectively). OS with ALN-pCR was significantly longer than that with ALN-mic (P = 0.004). There was no significant difference in DFS or OS between ALN-mac and ALN-mic. These data showed the clinical significance of microresidual metastases >0.2 mm after NAC in patients with cytologically proven axillary metastases. Conclusions  Using multislice sectioning, screening for ALN-mic after NAC was clinically important, and that for ALN-itc was not clinically essential.     

Axillary dissection in patients with preoperative positive nodal cytology: Genuine need or overtreatment?

Recent studies demonstrated the possibility to avoid axillary dissection (ALND) in selected patients with one or two metastatic nodes. Otherwise, patients with positive nodal ultrasound‐guided fine‐needle aspiration cytology (US‐FNAC) currently undergo ALDN. The aim of this study is to quantify the nodal burden in patients with positive US‐FNAC treated with ALND and to evaluate if clinical or pathological characteristics associated with low nodal involvement can be identified. This is a multicentric retrospective study involving 297 patients who underwent ALND because of a positive preoperative US‐FNAC. A total of 157 patients showed bulky axillary lymph nodes at diagnosis, and 70% of them had three or more metastatic nodes. One hundred and forty patients had a clinically negative axilla and in 50% of them, 4 or more metastatic nodes were found with axillary dissection. Overall, the median number of metastatic nodes was 5. Favorable pathological characteristics of tumors were found in patients with only one or two metastatic nodes: smaller primary tumor, a lower proportion of grade 3, invasive lobular carcinomas and a higher proportion of low‐Ki67 tumors. In the group of patients with clinically negative axilla and potentially meeting ACOSOG Z0011 criteria, 22 (31%) showed less than three metastatic axillary nodes. A preoperative positive axillary FNAC is associated with a metastatic nodal burden significantly higher than in patients with positive sentinel lymph node biopsy (SLNB). Nevertheless, about 30% of patients with cN0 axilla, positive axillary FNAC performed because of suspicious nodes on imaging, T1‐2 primary tumor and breast‐conserving surgery showed less than three metastatic axillary nodes, thus meeting ACOSOG Z0011 trial's criteria and therefore would be eligible for skipping ALND according to current guidelines.     

Predictors for extensive nodal involvement in breast cancer patients with axillary lymph node metastases

PurposeVarious prediction models have been developed to predict the risk of having no additional axillary metastases in patients with a positive sentinel lymph node biopsy (SLNB), thereby disregarding patients with a positive ultrasound-guided lymph node biopsy (UGLNB). However, in the post-Z0011 trial era it is important to identify all patients with extensive nodal involvement for whom axillary treatment might still be beneficial. Therefore, the aim of this study is to identify factors predicting extensive nodal involvement (≥3 positive nodes) in the axilla, with the emphasis on the method of axillary staging: node positivity by UGLNB versus SLNB.MethodsAll patients diagnosed with invasive breast cancer between January 2006 and December 2011 at the Máxima Medical Center were included. Univariate and multivariate logistic regression analyses were performed.ResultsWe included 302 cases, representing 301 node positive patients, of whom 177 cases had 1 or 2 positive lymph nodes and 125 cases had ≥3 positive lymph nodes. Multivariate analyses showed that a positive UGLNB (OR = 5.10; 95%CI = 2.78–9.36), lymphovascular invasion (OR = 3.60; 95%CI = 1.79–7.23) and a larger tumor size (OR = 1.03 per mm increase; 95%CI = 1.00–1.06) were significantly associated with extensive nodal involvement in patients with invasive breast cancer.ConclusionThis study shows that a positive axilla, determined by UGLNB, is the most important factor for predicting further extensive nodal involvement. Hence, the role of axillary staging by ultrasound should be redefined since it might play an important role in selecting patients who may still benefit from axillary treatment.     

MRI evaluation of axillary and intramammary lymph nodes in the postoperative period

Our study aimed to evaluate if breast‐conserving surgery and adjuvant treatment could affect the morphological features of axillary and intramammary lymph nodes on magnetic resonance imaging (MRI) in patients with invasive breast cancer and clinically negative axilla. In this single‐center study, we retrospectively evaluated 50 patients who had (a) breast‐conserving surgery, (b) clinically negative axilla, (c) preoperative MRI within 3 months before surgery, and (d) postoperative MRI within 12 months after surgery. Axillary and intramammary lymph nodes on postoperative MRI were identified and then compared with preoperative MRI by two breast radiologists with regards to the following: enlargement, cortical thickening, presence of fatty hilum, irregularity, heterogeneity, matting, and axillary lymph node asymmetry. Three hundred and two axillary and eight intramammary lymph nodes were evaluated. Enlargement and cortical thickening were seen in 5/50 (10%) patients in three axillary and two intramammary lymph nodes. None of the lymph nodes on postoperative MRI demonstrated occurrence of lack of fatty hilum, irregularity, heterogeneity, matting or axillary lymph node asymmetry. No evidence of recurrence was observed on 2‐year follow‐up. Lymph node enlargement and cortical thickening may be observed in a few patients in the postoperative period. Nevertheless, in patients with clinically negative axilla, these changes in morphology are often related to treatment rather than malignancy and favor short‐term follow‐up as an alternative to lymph node biopsy.     

Level III axillary lymph nodes involvement in node positive breast cancer received neoadjuvant chemotherapy

ObjectiveTo investigate the incidence, associated factors and prognosis of level III node involvement for breast cancer with positive axillary lymph nodes after neoadjuvant chemotherapy.MethodsA consecutive series of 521 node positive T_0–2 invasive breast cancer cases were included in this retrospective study. Axillary node metastases were proved by ultrasound guided needle biopsy (NB) if ultrasonographic abnormal node was detected or by sentinel node biopsy (SNB) if no abnormal node was detected. After 4 to 8 cycles of neoadjuvant chemotherapy (NCT）, axillary lymph nodes dissection included level III lymph nodes were completed for each case.ResultsThe pathologic complete response rate of axillary nodes was 31.1% (90/289) in NB positive subgroup. The incidence of residual positive level III lymph nodes were 9.0% (47/521). Multivariate analysis showed that node NB positivity (OR = 2.212, 95% CI: 1.022–4.787, P = 0.044), clinical tumor size >2 cm before NCT (OR = 2.672, 95% CI: 1.170–6.098, P = 0.020), and primary tumor non-response to neoadjuvant chemotherapy (OR = 1.718, 95% CI: 1.232–2.396, P = 0.001) were independent predictors of level III lymph nodes positivity. At median follow-up time of 30 months, the distant disease-free survival (DDFS) rate of level III node positive group was much lower than that of level III negative group (p = 0.011).ConclusionsAbout 9% of node positive T_0–2 breast cancer will have residual positive node in level III region after neoadjuvant chemotherapy. Node positivity proved by NB, large tumor size, and primary tumor non-response to neoadjuvant chemotherapy are independent predictors of level III lymph nodes positivity.     

Sentinel lymph node biopsy for breast cancer using methylene blue dye manifests a short learning curve among experienced surgeons: a prospective tabular cumulative sum (CUSUM) analysis

Background  

The benefits of sentinel lymph node biopsy (SLNB) for breast cancer patients with histologically negative axillary nodes, in whom axillary lymph node dissection (ALND) is thereby avoided, are now established. Low false negative rate, certainly with blue dye technique, mostly reflects the established high inherent accuracy of SLNB and low axillary nodal metastatic load (subject to patient selection). SLN identification rate is influenced by volume, injection site and choice of mapping agent, axillary nodal metastatic load, SLN location and skill at axillary dissection. Being more subject to technical failure, SLN identification seems to be a more reasonable variable for learning curve assessment than false negative rate.     

Axillary Staging Prior to Neoadjuvant Chemotherapy for Breast Cancer: Predictors of Recurrence

Background  The value of axillary staging prior to delivery of neoadjuvant chemotherapy (NEO) for breast cancer is controversial. Our goal was to analyze the prognostic and therapeutic impact of axillary staging on recurrence. Methods  The study cohort included 161 patients undergoing comprehensive evaluation by a multidisciplinary approach during the period 1996–2006. Clinicopathologic features were assessed before and after delivery of NEO. Patients with node-positive disease before NEO underwent a post-NEO axillary lymph node dissection at time of definitive breast surgery. Results  At presentation, median age was 49 years; mean tumor size was 45 mm. The axilla was negative in 45 (28.6%) patients. Of the 114 pre-NEO node-positive patients, 65 (57%) were staged histologically. At completion of NEO, partial or complete clinical response was observed in 90.6%; complete pathologic response occurred in 23.6%. Mean residual tumor size was 10.5 mm. Of the 112 initially node-positive patients, 36 (31.6%) had no residual axillary disease post NEO. At median follow-up of 38.1 months, 21.7% patients relapsed. The pre-NEO nodal status was the strongest predictor of treatment failure. A significant risk of distant relapse was based on nodal response to NEO: 8.1% in node-negative patients, 13.9% in the downstaged group, and 22.1% in the persistently positive group (P = 0.047). Delivery of nodal irradiation decreased local recurrence in the downstaged group (12.5% versus 3.7%, P = NS). Conclusion  Our experience suggests that comprehensive axillary staging with ultrasound and fine-needle aspiration (FNA) and sentinel lymph node biopsy prior to NEO is both prognostically and therapeutically important in predicting those patients at higher risk of recurrence.     

Three–Axillary Lymph Node Sampling for the Prediction of Nonsentinel Node Metastases in Breast Cancer Patients With Sentinel Node Metastases

Background In half of breast cancer patients with positive sentinel nodes, the sentinel nodes are the only metastatic nodes. Such patients have no more metastatic nonsentinel nodes and do not need to undergo axillary lymph node dissection. The purpose of this study was to investigate whether three–axillary lymph node sampling after sentinel node biopsy predicts the status of nonsentinel nodes in patients with sentinel node metastases. Methods Sentinel node biopsy was performed with dye and radioisotope. When the sentinel nodes were diagnosed as metastasis positive by using intraoperative imprint cytology, three–axillary lymph node sampling was performed, followed by axillary lymph node dissection. Results Of 47 cases with positive imprint cytology, 43 (91%) were diagnosed as metastasis positive on their final histological examination and were analyzed. The status of the sampled nodes was significantly associated with the status of nonsentinel nodes (P < .0001). Six (43%) of 14 patients with positive sampled nodes had at least 1 positive remaining node. Only 2 (7%) of 29 patients whose sampled nodes were negative were found to have additional nodal metastases. The sensitivity, specificity, and accuracy of the sampled nodes for the prediction of nonsentinel node metastases were 87.5%, 100%, and 95.3%, respectively. Conclusions We demonstrated that three-node sampling may be useful for predicting the status of nonsentinel nodes and avoiding axillary lymph node dissection in patients with only sentinel node metastases.     

High-resolution ultrasonographic features of axillary lymph node metastasis in patients with breast cancer

To determine ultrasound (US) features that most accurately predict the presence of axillary lymph node metastasis, we retrospectively analysed the results of preoperative US breast examinations of axillary lymph nodes in 425 consecutive patients who subsequently underwent surgery for invasive breast cancer. We compared the US findings with pathologic results for axillary lymph node metastasis. US features included length of the longest (L) and shortest (S) axes, L/S ratio, cortical thickness, presence of hilum and shape. The results of multivariate logistic regression analysis revealed that cortical thickness greater than 3 mm was the most accurate indicator, with 4.14 times increased risk of the presence of an axillary lymph node metastasis as compared to cortical thickness less than 3 mm. The absence of a hilum showed the highest specificity for axillary lymph node metastasis (94.6%), but low sensitivity.     

Development of a novel nomogram-based online tool to predict axillary status after neoadjuvant chemotherapy in cN+ breast cancer: A multicentre study on 1,950 patients

BackgroundType of axillary surgery in breast cancer (BC) patients who convert from cN + to ycN0 after neoadjuvant chemotherapy (NAC) is still debated. The aim of the present study was to develop and validate a preoperative predictive nomogram to select those patients with a low risk of residual axillary disease after NAC, in whom axillary surgery could be minimized.Patients and methods1950 clinically node-positive BC patients from 11 Breast Units, treated by NAC and subsequent surgery, were included from 2005 to 2020. Patients were divided in two groups: those who achieved nodal pCR vs. those with residual nodal disease after NAC. The cohort was divided into training and validation set with a geographic separation criterion. The outcome was to identify independent predictors of axillary pathologic complete response (pCR).ResultsIndependent predictive factors associated to nodal pCR were axillary clinical complete response (cCR) after NAC (OR 3.11, p < 0.0001), ER-/HER2+ (OR 3.26, p < 0.0001) or ER+/HER2+ (OR 2.26, p = 0.0002) or ER-/HER2- (OR 1.89, p = 0.009) BC, breast cCR (OR 2.48, p < 0.0001), Ki67 > 14% (OR 0.52, p = 0.0005), and tumor grading G2 (OR 0.35, p = 0.002) or G3 (OR 0.29, p = 0.0003). The nomogram showed a sensitivity of 71% and a specificity of 73% (AUC 0.77, 95%CI 0.75–0.80). After external validation the accuracy of the nomogram was confirmed.ConclusionThe accuracy makes this freely-available, nomogram-based online tool useful to predict nodal pCR after NAC, translating the concept of tailored axillary surgery also in this setting of patients.     

Influence of Tumor Histology on Preoperative Staging Accuracy of Breast Metastases to the Axilla

Histologic confirmation of axillary nodal metastases preoperatively avoids a sentinel node biopsy and enables a one step surgical procedure. The aim of this study was to establish the local positive predictive value of axillary ultrasound (AUS) and guided needle core biopsy (NCB) in axillary staging of breast cancer, and to identify factors influencing yield. A prospective audit of 142 consecutive patients (screening and symptomatic) presenting from 1st December 2008–31st May 2009 with breast lesions categorized R4–R5, who underwent a preoperative AUS, and proceeded to surgery was undertaken. Ultrasound‐guided NCB was performed on nodes radiologically classified R3–R5. Lymph node size, number, and morphological features were documented. Yield was correlated with tumor size, grade, and histologic type. AUS/NCB was correlated with post surgical pathologic findings to determine sensitivity, specificity, positive and negative predictive value of AUS and NCB. A total of 142 patients underwent surgery, of whom 52 (37%) had lymph node metastases on histology. All had a preoperative AUS, 51 (36%) had abnormal ultrasound findings. 46 (90%) underwent axillary node NCB of which 24 (52%) were positive. The smallest tumor size associated with positive nodes at surgery was 11.5 mm. The sensitivity of AUS was 65%. Specificity was 81%, with a positive predictive value (PPV) of 67% and negative predictive (NPV) value of 80%. Sensitivity of U/S‐guided NCB was 75%, with a specificity of 100%, PPV 100% and NPV 64%. Sensitivity of AUS for lobular carcinoma was 36% versus 76% for all other histologies. Sensitivity of NCB for lobular cancer was 33% versus 79% for all other histologies. The most significant factor producing discordance between preoperative AUS and definitive histologic evidence of lymph node metastasis was tumor type. Accurate preoperative lymph node staging was prejudiced by lobular histology (p < 0.0019).     

Should cervical ultrasonography be a routine staging investigation for lung cancer patients with impalpable cervical lymph nodes?

OBJECTIVES: Detection of cervical N3 lymph nodes is currently not a routine preoperative investigation for lung cancer patients. We designed a study to assess if the frequency and accuracy of detection of metastatic cervical lymph nodes using cervical ultrasonography (US) and fine needle aspiration (FNA) justify their routine use in all lung cancer patients with impalpable cervical lymph nodes. METHODS: Fifty patients with suspected and potentially operable non-small cell lung cancer were enrolled. Patients with palpable cervical lymph nodes were excluded. In addition to routine preoperative investigations, all patients received cervical US to determine the presence of cervical lymph nodes. Nodes suspicious of harboring malignancy according to a specific set of sonographic criteria (which include shape, echogenicity, nodal architecture, and vascular patterns) were subjected to biopsy by ultrasound-guided FNA. RESULTS: Normal cervical lymph nodes were detected by cervical US in 30 patients (60%). Cervical lymph nodes suspicious of harboring malignancy were detected in 10 patients (20%). FNA confirmed cervical nodal metastasis in four of these patients (8%). The TNM staging of two patients (4%) was revised up to stage IIIb as a result, excluding them from further surgery. Cost analysis suggests this technique to be cost-effective when used as a routine preoperative investigation to exclude patients from unnecessary surgical intervention. No mortality or complications were encountered in all patients. CONCLUSIONS: Cervical US and FNA is a safe and cost-effective method of evaluating the status of impalpable cervical lymph nodes in lung cancer patients. Further study is warranted to establish the role of cervical US and FNA in lung cancer staging algorithms.