Nodal Pathologic Complete Response Rates in Luminal Breast Cancer Vary by Genomic Risk

Background

Although an advantage of neoadjuvant chemotherapy (NAC) is eradication of axillary disease, nodal pCR rates are much lower for ER+/HER2? breast cancer than other subtypes. We sought to evaluate the association of genomic risk with nodal pCR in ER+/HER2? disease.

Methods

Patients with ER+/HER2? clinically-node-positive (cT0-cT4d/cN1-cN3/cM0) breast cancer treated with NAC and surgery 2010–2018 in the National Cancer Database were identified. Low genomic risk was classified as Oncotype Dx Recurrence Score (RS) 0–25, or Mammaprint 70-gene or RS coded as “Low.” High genomic risk included RS >25, or 70-gene or RS coded as “High.” Nodal pCR was compared between patients with high versus low genomic risk by using chi-square tests and multivariable logistic regression.

Results

Of 15,698 patients, genomic risk was available for 692 of 15,698 (4.4%). High genomic risk was similar between patients aged <50 years versus 50+ (50.8% vs. 57.3%, p = 0.10). Nodal pCR was higher in high genomic risk (25.0%) than low genomic risk (10.4%, p < 0.001). This difference was observed both for patients aged <50 years (29.9% vs. 9.8%) and aged ≥50 years (22.7% vs. 10.8%). On multivariable analysis adjusted for potential confounding variables, including age, grade, and PR status, genomic risk was independently associated with decreased odds of residual nodal disease (odds ratio 0.49, p = 0.002).

Conclusions

For patients with node-positive ER+/HER2? breast cancer treated with NAC, nodal pCR was highest in patients aged <50 years with high genomic risk tumors. In contrast, nodal pCR rates were low in patients with low genomic risk tumors, regardless of age. This information may help when counseling patients regarding axillary management.

     

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.     

Pathologic complete response after neoadjuvant chemotherapy in HER2-overexpressing breast cancer according to hormonal receptor status

ObjectiveFor patients with HER2-positive breast cancer, the prognostic impact of pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is unclear when stratified by hormonal receptor (HR) status; however, the impact of pCR on survival when stratified by hormonal receptor (HR) status is uncertain.Patients and methodsThis multicenter retrospective study investigated the predictors of pCR and its prognostic value in Japanese patients 366 HER2-positive breast cancer who received NAC. pCR was defined as no invasive residual tumor in the breast or axilla.ResultsMedian follow-up was 55 months. Multivariate analysis revealed that HR status (OR, 0.37; p < 0.001) was one of the independent predictors of pCR. Five-year recurrence-free survival was higher in HR-negative patients with pCR (93%) than in those without pCR (68%), and pCR was independently prognostic (hazard ratio, 0.32; p = 0.005). However, 5-year recurrence-free survival was not different between HR-positive patients with pCR (94%) and those without pCR (84%), and pCR was not significantly prognostic (hazard ratio, 0.53; p = 0.39). In addition, 5-year overall survivals were high and similar (97% in pCR, 94% in non-pCR). Among 204 patients treated with neoadjuvant trastuzumab, pCR was not significantly prognostic in the HR-positive group (hazard ratio, 0.63; p = 0.56).ConclusionOur study suggested that the HER2-positive HR-positive patients had a good prognosis despite the lower achievement rate of pCR, whose prognostic impact was smaller than that in the HER2-positive HR-negative patients. The treatment strategy for HER2-positive breast cancer can be stratified by HR status.     

Clinical impact of adjuvant radiation therapy delay after neoadjuvant chemotherapy in locally advanced breast cancer

Backgroundand Purpose: Post-operative radiation therapy (PORT) is usually indicated for patients with breast cancer (BC) after neoadjuvant chemotherapy (NAC) and surgery. However, the optimal timing to initiation of PORT is currently unknown.Material and methodsWe retrospectively evaluated data from patients with BC who received PORT after NAC and surgery at our institution from 2008 to 2014. Patients were categorized into three groups according to the time between surgery and PORT: <8 weeks, 8–16 weeks and >16 weeks.ResultsA total of 581 patients were included; 74% had clinical stage III. Forty-three patients started PORT within 8 weeks, 354 between 8 and 16 weeks and 184 beyond 16 weeks from surgery. With a median follow-up of 32 months, initiation of PORT up to 8 weeks after surgery was associated with better disease-free survival (DFS) (<8 weeks versus 8–16 weeks: HR 0.33; 95% CI 0.13–0.81; p = 0.02; <8 weeks versus >16 weeks: HR 0.38; 95% CI 0.15–0.96; p = 0.04) and better overall survival (OS) (<8 weeks versus 8–16 weeks: HR 0.22; 95% CI 0.05–0.90; p = 0.036; <8 weeks versus >16 weeks: HR 0.28; 95% CI 0.07–1.15; p = 0.08).ConclusionPORT started up to 8 weeks after surgery was associated with better DFS and OS in locally-advanced BC patients submitted to NAC. Our findings suggest that early initiation of PORT is critically important for these patients. However, the low numbers of patients and events in this study prevent us from drawing firm conclusions.     

The St. Gallen surrogate classification for breast cancer subtypes successfully predicts tumor presenting features,nodal involvement,recurrence patterns and disease free survival

AimsTo evaluate how the St. Gallen intrinsic subtype classification for breast cancer surrogates predicts disease features, recurrence patterns and disease free survival.Materials and methodsSubtypes were classified by immunohistochemical staining according to St. Gallen subtypes classification in a 5-tyre system: luminal A, luminal B HER2-neu negative, luminal B HER2-neu positive, HER2-neu non luminal or basal-like. Data were obtained from the records of patients with invasive breast cancer treated at our institution. Recurrence data and site of first recurrence were recorded. The chi(2) test, analysis of variance, and multivariate logistic regression analysis were used to determine associations between surrogates and clinicopathologic variables.ResultsA total of 2.984 tumors were classifiable into surrogate subtypes. Significant differences in age, tumor size, nodal involvement, nuclear grade, multicentric/multifocal disease (MF/MC), lymphovascular invasion, and extensive intraductal component (EIC) were observed among surrogates (p < 0.0001). After adjusting for confounding factors surrogates remained predictive of nodal involvement (luminal B HER2-neu pos. OR = 1.49 p = 0.009, non-luminal HER2-neu pos. OR = 1.61 p = 0.015 and basal-like OR = 0.60, p = 0.002) while HER2-neu positivity remained predictive of EIC (OR = 3.10, p < 0.0001) and MF/MC (OR = 1.45, p = 0.02). Recurrence rates differed among the surrogates and were time-dependent (p = 0.001) and site-specific (p < 0.0001).ConclusionThe St. Gallen 5-tyre surrogate classification for breast cancer subtypes accurately predicts breast cancer presenting features (with emphasis on prediction of nodal involvement), recurrence patterns and disease free survival.     

Differences in sensitivity to neoadjuvant chemotherapy among invasive lobular and ductal carcinoma of the breast and implications on surgery–A systematic review and meta-analysis

Meta-analysis of >87,000 patients demonstrates that patients with invasive lobular carcinoma of the breast are far less likely to achieve pCR of the breast or axilla compared to their ductal counterparts, receive less BCS and more frequently return positive margins.BackgroundNeoadjuvant chemotherapy (NACT) facilitates tumour downstaging, increases breast conserving surgery (BCS) and assesses tumour chemosensitivity. Despite clinicopathological differences in Invasive Ductal Carcinoma (IDC) and Invasive Lobular Carcinoma (ILC), decision making surrounding the use NACT does not take account of histological differences.AimTo determine the impact NACT on pathological complete response (pCR), breast conserving surgery (BCS), margin status and axillary pCR in ILC and IDC.MethodsA systematic review was performed in accordance with the PRISMA guidelines. Studies reporting outcomes among ILC and IDCs following NACT were identified. Dichotomous variables were pooled as odds ratios (ORs) with 95% confidence intervals_(CI) using the Mantel-Haenszel method. P-values <0.05 were statistically significant.Results40 studies including 87,303 (7596 ILC [8.7%]and 79,708 IDC [91.3%]) patients were available for analysis. Mean age at diagnosis was 54.9 vs. 50.9 years for ILC and IDC, respectively. IDCs were significantly more likely to achieve pCR (22.1% v 7.4%, OR: 3.03 [95% CI 2.5–3.68] p < 0.00001), axillary pCR (23.6% vs. 13.4%, OR: 2.01 [95% CI 1.77–2.28] p < 0.00001) and receive BCS (45.7% vs. 33.3%, OR 2.14 [95% CI 1.87–2.45] p < 0.00001) versus ILCs. ILCs were significantly more likely to have positive margins at the time of surgery (36% vs 13.5%, OR 4.84 [95% CI 2.88–8.15] p < 0.00001).ConclusionThis is the largest study comparing the impact of NACT among ILC and IDC with respect to pCR and BCS. ILC has different outcomes to IDC following NACT and incorporate it into treatment decisions and future clinical guidelines.     

Neo‐adjuvant chemotherapy and axillary de‐escalation management for patients with clinically node‐negative breast cancer

This study aimed to explore the optimal time of sentinel lymph node biopsy (SLNB) and neo‐adjuvant chemotherapy (NAC) and to assess the feasibility of selective elimination of axillary surgery after NAC in clinically node‐negative (cN0) patients. From April 2010 to August 2018, 845 patients undergoing surgery after NAC were included in this retrospective study to analyze the correlation between different clinicopathological characteristics of cN0 patients and negative axillary lymph node after NAC (ypN0). Among the 148 cN0 patients, 83.1% (123/148) were ypN0. The rates of ypN0 in patients with hormone receptor positive (HR+)/HER2?, HR+/HER2+, HR?/HER2+, and triple‐negative (TN) breast cancer were 75.4% (46/61), 82.6% (19/23), 85.2% (23/27), and 94.6% (35/37), respectively (P < 0.001). The rates of ypN0 in TN and HER2+ patients were 94.6% and 95.5%, which were significantly higher than that in HR+/HER2? patients (P < 0.05). Molecular subtypes, clinical stage, radiologic complete response, and pathologic complete response (bpCR) of the breast tumor correlated with ypN0 after full‐course NAC (P < 0.05). Molecular subtypes (OR = 2.374, P = 0.033), clinical stage (OR = 0.320, P = 0.029), and bpCR (OR = 0.454, P = 0.012) were independent predictors for ypN0. The optimal time of SLNB and NAC in cN0 patients might be different among different molecular subtypes: it would be preferable to perform SLNB prior to NAC for HR+/HER2? patients, and SLNB after NAC for TN and HER2+ patients to reduce the risk of axillary lymph node dissection. In view of the high ypN0 rate in cN0 patients, axillary surgical staging might be selectively eliminated, especially for HER2+ and TN patients.     

The use of ultrasound in the clinical re-staging of the axilla after neoadjuvant chemotherapy (NACT)

IntroductionUltrasound (US) is the imaging modality of choice for staging the axilla prior to surgery in patients with breast cancer (BC). High pathological complete response rates in the axilla after NACT mean a more conservative approach to surgery can be considered. Radiological re-staging is important in this decision making. After the presentation of results from ACOSOG Z1071 in December 2012, formal ultrasound re-assessment of the axilla after primary therapy was specifically requested in our institution. We report on the accuracy of axillary US (aUS) for identifying residual axillary disease post-NACT.MethodsData were collected on patients who had proven axillary disease prior to NACT and underwent axillary lymph node dissection after NACT between January 2013 and December 2015. Post-chemotherapy aUS reports and axillary pathology reports were classified as positive or negative for abnormal lymph nodes and for residual disease (cCR and pCR respectively).ResultsThe sensitivity and specificity of aUS was 71% and 88% respectively. The negative predictive value (NPV) was 83%. The false negative rate was 29%.ConclusionsAxillary ultrasound provides clinically useful information post-NACT, which will guide surgical decision-making. Patients with aUS-negative axillae are likely to have a lower false negative rate of SLNB after NACT (Boughey et al.). However, aUS does not replace the need to identify and biopsy the nodes which were proven to be positive prior to NACT.     

Predictive value of DCE-MRI for early evaluation of pathological complete response to neoadjuvant chemotherapy in resectable primary breast cancer: A single-center prospective study

ObjectiveThis study proposed to establish a predictive model using dynamic enhanced MRI multi-parameters for early predicting pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast cancer.MethodsIn this prospective cohort study, 170 breast cancer patients treated with NAC were enrolled and were randomly grouped into training sample (136 patients) and validation sample (34 patients). DCE-MRI parameters achieved at the end of the first cycle of NAC were screened to establish the predictive model by using multivariate logistic regression model according to pCR status. Receiver operating characteristic curves were conducted to assess the predictive capability. The association between MRI-predicted pCR and actual pCR in survival outcomes was estimated by using the Kaplan–Meier method with log-rank test.ResultsMultivariate analysis showed ΔAreamax and ΔSlopemax were independent predictors for pCR, odds ratio were 0.939 (95%CI, 0.915 to 0.964), and 0.966 (95%CI, 0.947 to 0.986), respectively. A predictive model was established using training sample as “Y = −0.063*ΔAreamax − 0.034*ΔSlopemax”, a cut-off point of 3.0 was determined. The AUC for training and validation sample were 0.931 (95%CI, 0.890–0.971) and 0.971 (95%CI, 0.923–1.000), respectively. MRI-predicted pCR patients showed similar RFS (p = 0.347), DDFS (p = 0.25) and OS (p = 0.423) with pCR patients.ConclusionThe multi-parameter MRI model can be potentially used for early prediction of pCR status at the end of the first NAC cycle, which might allow timely regimen refinement before definitive surgical treatment.     

Impact of Neoadjuvant Chemotherapy on Nodal Disease and Nodal Surgery by Tumor Subtype

Background

Neoadjuvant chemotherapy (NAC) is known to downstage disease in the breast and increase breast conservation. It can also decrease nodal disease extent. We evaluated the impact of NAC on nodal positivity, nodal burden, and nodal surgery by tumor subtype.

Methods

All cT1–4c breast cancers from 2010 to 2014 in the National Cancer Database were evaluated, comparing patients receiving NAC with those undergoing primary surgery (PS). Rates of pathologic node-negative status (pN0) and sentinel lymph node (SLN) surgery (1–5 nodes) were compared using chi-square tests, and adjusted odds ratios (OR) were estimated.

Results

Of 461,549 patients, 36,715 (8.0%) received NAC and 424,834 (92.0%) had PS. In cN0 patients, pN0 rates were higher in NAC compared with PS patients in ER?/HER2+ [93.2 vs. 79.0%, odds ratio (OR) 3.64, p < 0.001], ER?/HER2? (89.9 vs. 85.2%, OR 1.55, p < 0.001), and ER+/HER2+ (84.7 vs. 78.3%, OR 1.54, p < 0.001). Patients with cT2–3, N0 tumors had significantly higher rate of SLN surgery for NAC versus PS for each biologic subtype except for ER+/HER2? tumors, amongst which this was true only for T3 tumors. In cN1–3 patients, pN0 rates after NAC were 61.3% in ER?/HER2+, 47.7% in ER+/HER2+, 47.3% in ER?/HER2?, and 20.2% in ER+/HER2? and SLN surgery was highest in ER?/HER2+ (28.9%, p < 0.05 versus other subtypes).

Conclusion

NAC increases rates of pN0 among cN0 patients compared with PS. Among cN+ patients, 20–61% undergoing NAC convert to pN0 depending on tumor type, with lowest nodal response in ER+/HER2? disease. Use of NAC results in less extensive axillary surgery than in patients treated with PS in both cN0 and cN+ disease.

     

Development and external validation of a nomogram to predict four or more positive nodes in breast cancer patients with one to three positive sentinel lymph nodes

ObjectiveTo develop a nomogram for predicting the possibility of four or more positive nodes in breast cancer patients with 1–3 positive sentinel lymph nodes (SLN).Materials and methodsRetrospective analysis of data of patients from two institutions was conducted. The inclusion criteria were: invasive breast cancer; clinically node negative; received lumpectomy or mastectomy plus SLN biopsy followed by axillary lymph node dissection (ALND); and pathologically confirmed T1-2 tumor, with 1–3 positive SLNs. Patients from one institution formed the training group and patients from the other the validation group. Univariate and multivariate analyses were performed to identify the predictors of four or more positive nodes. These predictors were used to build the nomogram. The area under the receiver operating characteristic curve (AUC) was calculated to assess the accuracy of the model.ResultsOf the 1480 patients (966 patients in the training group, 514 in the validation group), 306 (20.7%) had four or more positive nodes. Multivariate stepwise logistic regression showed number of positive (p < .001) and negative SLN (p < .001), extracapsular extension (p < .001), pT stage (p = .016), and tumor location in outer upper quadrant (p = .031) to be independent predictors of four or more positive nodes. The nomogram was built using these five factors. The AUC was 0.845 in the training group and 0.804 in the validation group.ConclusionThe proposed nomogram appears to accurately estimate the likelihood of four or more positive nodes and could help radiation oncologists to decide on use of regional nodal irradiation (RNI) for breast cancer patients with 1–3 positive nodes but no ALND.     

pCR rates in patients with bilateral breast cancer after neoadjuvant anthracycline-taxane based-chemotherapy – A retrospective pooled analysis of individual patients data of four German neoadjuvant trials

PurposePatients with bilateral breast cancer (BBC) are usually excluded from participating in clinical trials and little is known about the response and outcome of BBC to neoadjuvant chemotherapy compared to unilateral BC (UBC).MethodsWe prospectively captured the information on patients with BBC in our database treated within four neoadjuvant chemotherapy trials and collected retrospectively the rate of pathological complete response (pCR) defined as ypT0 ypN0, ypT0/is ypN0, ypT0 ypNX, clinical and histologic parameters. Synchronous carcinoma in the contralateral breast was considered as the non-indicator lesion. Patients with UBC only treated within the same neoadjuvant trials performed the control group.ResultsFrom the 6727 patients treated within 4 German neoadjuvant trials 119 (1.8%) patients have been identified with the diagnosis of BBC. The pCR rate (ypT0 ypN0) was 12.6% in the non-indicator lesion group versus 10.9% the indicator lesion group versus 20.9% for patients with unilateral disease (p = 0.003). There were more advanced tumor stages and positive axillary lymph nodes in the indicator lesion than in the nonindicator lesion or in UBC. In 52.5% the molecular subtype was identical between indicator and non-indicator lesion with more triple negative and HER2 positive BC in the group of UBC. The disease free survival rate (DFS) was 25.8% for patients with UBC versus 39.6% for patients with BBC.ConclusionThe selection for the indicator lesion was based on tumor size, nodal status and inclusion criteria. Patients with BBC patients had a lower pCR rate and a lower DFS.     

Lower lymph node yield in axillary lymph node dissection specimens in breast cancer patients receiving neoadjuvant chemotherapy: Quality concern or treatment effect?

Axillary lymph node dissection (ALND) specimens should have at least ten-lymph nodes for examination according to established guidelines. Nonetheless, recent evidence suggests that neoadjuvant chemotherapy (NAC) results in fewer nodes in the specimen. We sought to examine if NAC patients have lower lymph node yield from ALND specimens and whether the number of lymph nodes in the specimen is correlated with pathologic complete response (pCR). Using the National Cancer Database (NCDB), a study cohort of female patients with node-positive, non-metastatic invasive breast cancer diagnosed from 2012 to 2015 was identified. The axillary lymph node retrieval count was compared in NAC and non-NAC patients and then correlated with pCR. A multivariable analysis was performed to identify factors that were associated with less than ten-lymph nodes in the ALND pathologic specimen. Of 56,976 patients identified, 27,197 (48%) received neoadjuvant chemotherapy; 29,779 (52%) did not. NAC patients failed to meet the ten-lymph node minimum in the ALND specimen more often than non-NAC patients (35% vs. 27%, p < 0.001). NAC patients with fewer than ten-lymph nodes were more likely to have a pCR than those with ten or more (22% vs. 16%, p < 0.001). On multivariable analysis, pCR of the primary tumor and receptor status were found to be independent predictors of having fewer than ten-lymph nodes in the ALND specimen. Node-positive breast cancer patients that underwent NAC were more likely to not meet the ten-lymph node standard. However, NAC patients who did not meet the minimum were also more likely to have a pCR compared to NAC patients who did. This suggests lower lymph node yield may not truly be a marker of lower quality surgery but rather a potential marker of NAC treatment effect.     

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.     

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.     

Incidence,risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China.MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively.ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment.ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.     

Pathological response and survival after neoadjuvant therapy for breast cancer: A 30-year study

Purpose of the researchHER2-positive and triple-negative breast cancer (TNBC) still have a poor prognosis. Pathological complete response (pCR) is usually considered a surrogate marker for outcome. The aim of this study was to reconsider these parameters on a large population after a long follow-up. 348 patients with unilateral breast cancer who received neoadjuvant treatment at our institution over 30 years were included.ResultsPatients were classified according to hormonal receptors (HR) and HER2. Median follow-up was 7 years. pCR was significantly lower in HR+/HER2? tumors (P < 0.0001). The 7-year OS rates were 76.1% (HR+/HER2?), 60.1% (TNBC), 72.4% (HR+/HER2+), and 49.9% (HR?/HER2+). Disease-free survival (DFS) and OS differed significantly according to pCR. Among HER2+ patients, pCR rate, DFS and OS were greater with trastuzumab.ConclusionsTNBC and HR?/HER2+ tumors have the worst outcome. pCR remains a significant prognostic factor. Trastuzumab strongly improves pCR and survival in HER2+ tumors.     

Simple oncoplastic breast defect closure improves long-term cosmetic outcome of breast conserving surgery for breast cancer: A randomised controlled trial

IntroductionBreast conserving surgery (BCS) is associated with unsatisfactory cosmetic outcomes in up to 30% of patients, carrying psychological and quality-of-life implications. This study compares long-term cosmetic outcomes after BCS for breast cancer with v without simple oncoplastic defect closure.MethodsA randomised controlled trial was performed, recruiting patients who underwent BCS over four years and randomising to the “reshaping” group (closure of excision defect with mobilised breast tissue; n = 124) and to the “control” group (no attempt at defect closure; n = 109). The estimated excision volume (EEV) was <20% of breast volume (BV) in both groups. Photography and breast retraction assessment (BRA) were recorded preoperatively. Cosmetic outcomes were blindly assessed annually for five years by BRA, panel assessment of patients, and body image questionnaire (BIQ).ResultsThere were no significant differences between the reshaping and control groups in mean age (52.4 v 53.0; p = 0.63), body mass index (27.8 v 27.7; p = 0.80), margin re-excision (9 v 9; p = 0.78), mean BV (562.5 v 590.3 cc; p = 0.56), mean EEV (54.6 v 60.1 cc; p = 0.14), mean EEV/BV ratio (11.2 v 11.0; p = 0.84), or mean specimen weight (52.1 v 57.7 g; p = 0.24). Reshaping group patients had significantly better outcomes compared to control group patients in terms of mean BRA (0.9 v 2.8; p < 0.0001), achieving a score of “good” or “excellent” by panel assessment at 5 years (75.8% v 48%, p < 0.0001), body image questionnaire top score at 5 years (66.9% v 35.8%; p = 0.0001).ConclusionsSimple oncoplastic closure of defects after breast-conserving surgery improves long-term objective and subjective cosmetic outcomes.