Changes in Ki-67 in Residual Tumor and Outcome of Primary Inflammatory Breast Cancer Treated With Trimodality Therapy

BackgroundLimited data are available on the prognostic role of Ki-67 changes in residual tumors after neoadjuvant chemotherapy in primary inflammatory breast cancer (IBC) patients treated with trimodality therapy. This study aims to evaluate changes in Ki-67 associated with disease-free survival (DFS) and overall survival (OS) in IBC patients without pathological complete response.Patients and MethodsWe identified a cohort of primary IBC patients with matched pre- and posttreatment samples treated with anthracycline and taxane-based regimen. All patients had a pathological evaluation, including ER, PR, HER2 status, and Ki-67 expression performed both at diagnostic core biopsy and at final surgery. Kaplan–Meier and Cox proportional hazards methods were used to assess DFS and OS rates and their relationship with clinicopathological features.ResultsTwo hundred and ten patients with stage III IBC were included. Sixty-three percent of residual tumors showed a decrease in Ki-67 positivity by at least 1%. The decrease of Ki-67 significantly correlated with better DFS (p = .001) and OS (P = .010) compared with no decrease, particularly in the luminal B-like and HER2-positive subgroups. The multivariate analysis showed that the decrease in Ki-67 level had a significant positive predictive value on DFS (HR = 0.47, 95% CI: 0.33-0.67; P< .001) and OS (HR = 0.59, 95% CI: 0.36-0.82; P= .004) in all IBC patients.ConclusionThe decrease of Ki-67 expression after neoadjuvant chemotherapy has a prognostic significance in IBC patients with residual disease. Evaluation of Ki-67 changes may help to identify subgroups of patients with worse outcome to receive novel treatment in this setting.     

Aggressive Subsets of Metastatic Triple Negative Breast Cancer

BackgroundRelative to other metastatic breast cancer subtypes, metastatic triple-negative breast cancer (mTNBC) has a shorter duration of response to therapy and worse overall survival. Among patients with mTNBC, it is hypothesized that inflammatory breast cancer (IBC) and young women have particularly aggressive phenotypes. We investigated clinical and cell-free DNA (cfDNA) characteristics of inflammatory-mTNBC and young-mTNBC.Patients and MethodsWe evaluated 158 patients with mTNBC who were stratified into 3 groups: (1) IBC; (2) patients aged 45 years or younger at primary diagnosis without IBC (non-IBC young); and (3) patients over age 45 at diagnosis without IBC. We evaluated clinicopathologic characteristics, sites of metastasis, survival outcomes, and the fraction of DNA in circulation derived from tumor (TFx).ResultsAnalysis of metastatic sites revealed that young patients without IBC had the most frequent lung metastases (P = .002). cfDNA analyses of first sample showed that TFx was highest in the non-IBC young group but not elevated in the IBC group (analysis of variance P = .056 for first TFx). Individually, median overall survival from metastatic diagnosis for the IBC group was 15.2 months; for the non-IBC young group, 21.2 months, and for the non-IBC over 45 group, 31.2 months. Patients with IBC and young patients without IBC had worse prognosis relative to patients over 45 without IBC (log-rank P = .023).ConclusionsAmong patients with mTNBC in this single-institution cohort, patients with IBC and young patients without IBC had significantly worse overall survival compared with patients over 45 without IBC. Young patients without IBC had significantly higher cfDNA TFx, whereas patients with IBC did not have elevated TFx despite a poor prognosis. These findings demonstrate that further analyses of mTNBC subsets are warranted.     

Circulating tumor cells in metastatic inflammatory breast cancer

BackgroundInflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Circulating tumor cells (CTCs) are an independent prognostic factor in metastatic breast cancer. The aim of this study was to assess the prognostic value of baseline CTCs in metastatic IBC patients.Patients and methodsThis retrospective study included 42 metastatic IBC and 107 metastatic non-IBC patients treated with first- or second-line chemotherapy from January 2004 to December 2007 at MD Anderson Cancer Center. CTCs were detected and enumerated before patients started chemotherapy using the CellSearch™ system.ResultsTen (23.8%) IBC patients versus 48 (44.9%) non-IBC patients had baseline CTCs ≥5 per 7.5 ml of peripheral blood. IBC patients had a lower mean ± SEM CTCs than non-IBC patients (7.6 ± 2.9 versus 34.2 ± 9.1; P = 0.02). The estimated median overall survival was 26.5 versus 18.3 months (P = 0.68) in IBC patients and 37.4 versus 18.3 months (P = 0.016) in non-IBC patients with CTCs <5 and CTCs ≥5, respectively.ConclusionsMetastatic IBC patients had a lower prevalence and fewer CTCs in comparison to metastatic non-IBC patients. Survival of metastatic IBC patients with <5 CTCs was not significantly better than that of patients with ≥5 CTCs. Further research is warranted with prospective assessment of CTCs in IBC patients and their biological characterization.     

Complete circumferential lymphadenectomy around the superior mesenteric artery with preservation of nerve plexus reduces locoregional recurrence after pancreatoduodenectomy for resectable pancreatic ductal adenocarcinoma

BackgroundEvaluation of recurrence pattern and risk factors for recurrence are essential for good rates of survival after upfront pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC).MethodsThis retrospective study included 167 consecutive patients who underwent upfront PD for resectable PDAC between 2000 and 2018. Postoperative recurrences were classified into three patterns according to initial recurrence site: isolated locoregional, isolated distant, and simultaneous locoregional and distant recurrences.ResultsThis study found 114 patients who developed postoperative recurrence (68.3%), including 37 patients with isolated locoregional recurrence (32.5%), 67 patients with isolated distant recurrence (58.8%), and 10 patients with simultaneous locoregional and distant recurrences (6.0%). When locoregional recurrence was classified based on the location of recurrent lesions, locoregional recurrence most commonly occurred around the superior mesenteric artery (SMA) (70.2%), followed by around the hepatic artery (25.5%) and in the paraaortic region (14.9%). Multivariate analyses showed that complete circumferential lymphadenectomy around the SMA, including not only the right side, but also the left side, was an independent factor for reduction of locoregional recurrence (P = 0.019, odds ratio [OR]: 2.217). Lymph node metastasis was an independent risk factor for both locoregional (P < 0.001, OR: 3.686) and distant recurrences (P < 0.001, OR: 4.315). Non-completion of postoperative adjuvant therapy was a risk factor for distant recurrence (P < 0.001, OR: 3.748).ConclusionBased on our data, complete circumferential lymphadenectomy around the SMA might contribute to local control, and multidisciplinary treatment including neoadjuvant therapy might be needed for resectable PDAC with high risk for recurrence.     

Inflammatory breast cancer (IBC) and patterns of recurrence: understanding the biology of a unique disease

BACKGROUND: Inflammatory breast cancer (IBC) is the most aggressive manifestation of primary breast cancer. The authors compared the prognostic features of IBC and non-IBC locally advanced breast cancer (LABC) to gain insight into the biology of this disease entity. METHODS: This retrospective analysis consisted of 1071 patients, comprising 240 patients with IBC and 831 patients with non-IBC LABC who were enrolled in 10 consecutive clinical trials (5 from each disease group). All patients received similar multidisciplinary treatment. The authors measured time to disease recurrence for each individual site from the start of treatment to the date of disease recurrence or last follow-up (recurrence-free survival) and overall survival rates to the date of last follow-up or death. RESULTS: The median follow-up period was 69 months (range, 1-367 months). Pathologically complete response rates were 13.9% and 11.7% in the IBC and non-IBC LABC groups, respectively (P = .42). The 5-year estimates of cumulative incidence of recurrence were 64.8 % and 43.4% (P < .0001), respectively, for IBC and non-IBC LABC. IBC had significantly higher cumulative incidence of locoregional recurrence and distant soft-tissue and bone disease. The 5-year overall survival (OS) rate was 40.5% for the IBC group (95% CI, 34.5%-47.4%) and 63.2% for the non-IBC LABC group (95% CI, 60.0%-66.6%; P < .0001). CONCLUSIONS: IBC was associated with a worse prognosis and a distinctive pattern of early recurrence compared with LABC. These data suggested that investigating factors affecting "homing" of cancer cells may provide novel treatment strategies for IBC.     

Evaluation of lymphangiogenic factors, vascular endothelial growth factor d and e-cadherin in distinguishing inflammatory from locally advanced breast cancer

BackgroundInflammatory breast cancer (IBC) is an aggressive form of breast cancer that on presentation resembles locally advanced breast cancer (LABC). This study identified molecular features of IBC and LABC to investigate pathogenesis.Materials and MethodsThis study involved 100 IBC cases identified in a national IBC registry and 107 non-IBC LABC cases from the National Cancer Institute's Cooperative Breast Cancer Tissue Resource (CBCTR). Vascular endothelial growth factor D (VEGF-D) and E-cadherin levels and lymphatic vessel density (LVD) measured by podoplanin staining were examined by immunohistochemistry on paraffin-embedded tumor specimens. Intralymphatic tumor emboli (ILTE) were assessed in IBC and non-IBC tumors. IBC cases diagnosed by clinicians but not meeting the case definitions of the American Joint Committee on Cancer (AJCC) or the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute (NCI)(designated atypical IBC) were compared with AJCC- and/or SEER-defined cases (designated classic IBC).ResultsE-cadherin levels were significantly higher in classic IBC cases compared with non-IBC cases (P = .031), whereas compared with classic IBC, patients with non-IBC LABC had significantly higher LVD (P = .0017) and VEGF-D levels (P < .0001). ILTE was marginally greater in classic IBC than in non-IBC (P = .046). The profile of laboratory values in atypical IBC cases more closely resembled those fitting classic IBC than LABC.ConclusionE-cadherin levels, LVD, VEGF-D expression, and to a lesser extent, ILTE differed between classic IBC and non-IBC LABC. The similarity of laboratory results between atypical IBC and classic IBC vs. LABC suggests the need for broadening both the AJCC and SEER case definitions for this disease.     

Aggressive Surgical Excision of Supraclavicular Lymph Node Did Not Improve the Outcomes of Breast Cancer With Supraclavicular Lymph Node Involvement (KROG 16-14)

IntroductionThe purpose of this study was to evaluate the outcomes of upfront surgery followed by radiation therapy (RT) for ipsilateral supraclavicular (SCN) and/or internal mammary (IMN) node-positive breast cancer.Materials and MethodsOne hundred fifty-eight patients were included; among these, 91 patients were SCN-positive, 54 were IMN-positive, and 13 were SCN- and IMN-positive. Patients underwent breast conserving surgery (n = 74) or mastectomy (n = 84) followed by systemic therapy, and adjuvant RT to whole breast/chest wall with or without regional nodal RT. Regarding regional treatments for SCN and IMN, SCN excision was performed in 59 (37.3%) patients, IMN excision in 10 (6.3%) patients, SCN RT in 143 (90.5%) patients, and IMN RT in 68 (43.0%) patients.ResultsThe median duration of follow-up was 72 months (range, 7-182 months). There were 20 locoregional recurrences and 45 distant metastases. In-field failure was observed only in SCN (n = 8), and 6 of these patients initially underwent SCN excision. The 5-year locoregional recurrence-free survival, disease-free survival (DFS), and overall survival rates were 87.3%, 71.6%, and 89.7%, respectively. Neither SCN excision nor SCN RT dose ≥ 54 Gy improved locoregional control (P = .927 and P = .693, respectively) or DFS (P = .394 and P = .686, respectively). Having ≥ 10 involved axillary lymph nodes was the only independent prognosticator for DFS after adjusting for covariates (P = .003).ConclusionRegional control rate in initially involved SCN and/or IMN was acceptable in patients treated with upfront surgery followed by systemic therapy plus adjuvant RT. More aggressive regional therapy such as SCN excision did not improve locoregional control or survival.     

Mucinous Adenocarcinoma Predicts Poor Response and Prognosis in Patients With Locally Advanced Rectal Cancer: A Pooled Analysis of Individual Participant Data From 3 Prospective Studies

PurposeTo evaluate the predictive implications and prognosis of mucinous adenocarcinoma (MAC) in locally advanced rectal cancer (LARC) with intensified neoadjuvant treatment.MethodsIndividual patient data of LARC patients from 3 prospective clinical trials was analyzed. Neoadjuvant treatment regimens comprised chemoradiotherapy (CRT) with fluorouracil (5-FU) or mFOLFOX6, neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI. The postoperative pathological result, local recurrence and disease-free survival (DFS) were retrospectively analyzed in patients with MAC and adenocarcinoma (AC) with neoadjuvant treatment.ResultsTotally, 743 patients were recruited, with 620 patients eligible for analysis. Fifty-three (8.5%) patients were MAC. The pathological complete response (pCR) rate and tumor downstaging rate (ypStage 0-I) between MAC and AC patients was 7.5% vs. 22.0% (P = .01) and 20.8% vs. 48.7% (P < .001), respectively. Among patients receiving preoperative CRT with 5FU or mFOLFOX6, the pCR rate and tumor downstaging rate between MAC and AC patients was 11.1% vs. 27.3% (P = .03) and 23.7% vs. 52.6% (P = .001), respectively. Regarding neoadjuvant chemotherapy alone with mFOLFOX6 or mFOLFOXIRI, the pCR rate and tumor downstaging rate was 0 vs.13.2% (P = .11) and 11.8% vs. 42.5% (P = .03) between MAC and AC group, respectively. With the median follow-up time of 38.9 months, the 3-year DFS and 3-year locoregional recurrence rate was 58.4% vs. 77.6% (P = .02) and 26.0% vs. 5.7% (P = .001) in the MAC and AC group, respectively. MAC (hazard ratio [HR] 1.85, 95% confidence interval [CI], 1.15-2.98), PNI (HR 3.23, 95% CI, 1.85-5.72) and LVI (HR 2.04, 95% CI, 1.02-4.08) were independent prognosis factors and were associated with worse DFS.ConclusionsPatients with MAC of the rectum are associated with a lower pCR rate and tumor downstaging rate, higher incidence of local recurrence, and poorer DFS with neoadjuvant treatment.     

Outcomes of Patients With Breast Cancer Who Present With Ipsilateral Supraclavicular or Internal Mammary Lymph Node Metastases

BackgroundThe prognostic implications of internal mammary (IM) and supraclavicular (SC) node involvement in locally advanced breast cancer is still unclear.Patients and MethodsWe evaluated 107 patients with IM (n = 65) or SC (n = 42) node involvement who underwent operation at the European Institute of Oncology between 1997 and 2009 to assess their prognostic features. We subsequently analyzed matched cohorts, using the 107 patients as cases and another group of patients as a control cohort, to evaluate prognostic differences between patients with and those without IM or SC node involvement.ResultsFive-year disease-free survival (DFS) was 84% in IM vs. 38.8% in SC node involvement (P < .0001), and 5-year overall survival (OS) was 96.9% in IM node vs. 57.1% in SC node involvement (P < .0001). No difference in outcome was found between patients with and controls without IM node involvement. Conversely, a statistically significant difference in DFS and locoregional recurrence was observed in patients with SC node involvement compared with controls without SC node involvement.ConclusionSC node involvement correlated with a significantly poorer outcome in patients with locally advanced breast cancer. Adequate staging, including biopsy of suspicious locoregional ipsilateral lymph nodes, is mandatory in these patients. Patients with IM or SC node involvement should be treated with curative intent using combined-modality treatments.     

Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease

BACKGROUND: The objectives of this study were to summarize a single-institution experience in treating patients with inflammatory breast carcinoma (IBC) using trimodality therapy and to identify prognostic factors for outcome. METHODS: Sixty-one women underwent radiation therapy with curative intent for IBC between 1982 and 2001. All but five women received trimodality therapy. Neoadjuvant chemotherapy was given to the majority of women (n = 43 patients), although some received "up-front" surgery as first therapy (n = 18 patients). RESULTS: With a median potential observation time after diagnosis of 14 years, freedom from locoregional disease progression was 78%, freedom from distant metastasis was 45%, and the cause-specific survival rate was 47% at 5 years. Approximately 40% of the 56 patients who received trimodality therapy remained free of disease. Multivariate analysis demonstrated three factors that were found to be associated significantly with improved cause-specific survival: pathologic tumor size < 4 cm (P = 0.0001), up-front surgery (P = 0.0078), and local disease control (P = 0.0003). Factors that were found to be associated with better freedom from locoregional disease progression were pathologic tumor size (< 4 cm; P = 0.0157), age (> 55 years; P = 0.0596), and radiation dose (> or = 60 grays [Gy]; P = 0.0621). CONCLUSIONS: IBC is an aggressive disease that is treated effectively in select patients by multimodality therapy. Patient outcomes may be improved with therapies that result in better local and systemic control. Further studies are warranted to address the optimal sequence of trimodality therapy and the optimal administration of each agent.     

Patterns of Failure in Women Who Have Residual Nodal Disease After Neoadjuvant Chemotherapy for Breast Cancer According to Extent of Lymph Node Surgery

BackgroundOptimal surgical management of limited axillary nodal disease following neoadjuvant chemotherapy (NAC) for breast cancer is evolving. Concerns exist with respect to leaving residual disease in the axilla when omitting axillary lymph node dissection (ALND) in this setting. We sought to determine whether extent of nodal surgery altered patterns of failure and patient outcomes.Patients and MethodsWe identified 70 patients with breast cancer who were confirmed cN0 after NAC yet had residual nodal disease (ypN1) on sentinel lymph node biopsy (SLNB). Twenty-eight patients underwent SLNB alone and 42 underwent SLNB+completion (c)ALND in a non-randomized fashion. Most (n = 65) patients underwent adjuvant regional nodal irradiation (RNI). Detailed patterns of failure data were obtained for each patient.ResultsThe median follow-up was 43.5 months. There were 30 (43%) recurrences. Of these, 5 were isolated locoregional failures, and 24 were distant failures. There were no significant differences in local (P = .13), regional (P = .62), or distant (P = .47) failure between patients who underwent SLNB alone versus SLNB+cALND. Seventeen (24%) patients died. Overall survival was similar in both groups with median overall survival not reached for those who underwent SLNB and 109 months for those who underwent SLNB+cALND (P = .45).ConclusionsThere were no differences in patterns of recurrence among patients with 1 to 3 involved lymph nodes after NAC who underwent SLNB alone versus SLNB+cALND in the setting of RNI. We await the results of ongoing, prospective clinical trials to confirm the relative merits of RNI in lieu of cALND in these patients.     

Locoregional and Distant Outcomes in Women With cT1-3N1 Breast Cancer Treated With Neoadjuvant Chemotherapy With or Without Adjuvant Radiotherapy

BackgroundWe evaluated the impact of postmastectomy radiotherapy (PMRT) or supraclavicular radiation therapy (SCV RT) in women with cT1-3N1 breast cancer (BC) who became node negative (ypN0) after neoadjuvant chemotherapy (NAC).Patients and MethodsWe retrospectively reviewed 485 women treated with NAC for BC between 2005 and 2019. Radiation treatment fields were reviewed in detail. Pathologic complete response (pCR) was defined as ypT0/Tis ypN0. Patients who had residual nodal disease were defined as ypN+. Those who achieved complete response in the lymph nodes but not in the breast were defined as ypT+ypN0.ResultsAfter excluding patients with cT4 and cN0 disease at diagnosis, a total of 185 patients with cT1-3N1 BC were included. Patients were more likely to receive PMRT if they had ypN+ disease (P < .001) and/or lymphovascular invasion (P = .03). Patients who underwent lumpectomy were more likely to receive SCV RT if they did not achieve pCR (P = .04) and/or if they had ypN+ disease (P = .01). The 5-year rates of locoregional recurrence (LRR) were 15% for all patients, 14% for patients who attained ypT+ypN0, and 5% for patients who achieved pCR. Of ypT+ypN0 patients (n = 98), 53 received PMRT or SCV RT and 45 did not. For these patients, there were no differences in LRR based on whether a patient did or did not receive PMRT or SCV RT (P = .23).ConclusionRecommendations for or against PMRT or SCV RT after NAC vary based on final pathologic response. We await the results of ongoing randomized clinical trials to help guide clinical decision making in this context.     

Extended Adjuvant Therapy With Aromatase Inhibitors for Early Breast Cancer: A Meta-analysis of Randomized Controlled Trials

BackgroundAromatase inhibitors (AIs) are widely used for early breast cancer, whereas the efficacy and safety of extended AI adjuvant therapy compared with shorter AI therapy, observation, or placebo remains controversial. We conducted a quantitative meta-analysis to summarize available randomized controlled trials (RCTs) regarding the efficacy and safety of extended AI therapy for early breast cancer.Materials and MethodsWe systematically searched PubMed, EmBase, and the Cochrane library to select studies published through March 2018. Studies designed as RCTs and that investigated overall survival (OS) or disease-free survival (DFS) for extended AI and shorter AI therapy, observation, or placebo were included. Hazard ratio (HR) and relative risk (RR) with 95% confidence intervals (CIs) were employed to pool analysis according to data type.ResultsWe identified 7 RCTs that involved 16,926 patients with early breast cancer. The summary HRs indicated that extended treatment with AIs was not associated with OS (HR, 0.95; 95% CI, 0.82-1.10; P = .488), whereas it could significantly improve DFS as compared with shorter AI therapy, observation, or placebo (HR, 0.75; 95% CI, 0.66-0.86; P < .001). Treatment with extended AIs significantly reduced contralateral breast cancer recurrence (RR, 0.46; 95% CI, 0.34-0.64; P < .001), whereas it has no significant effect on distant metastatic recurrence (RR, 0.80; 95% CI, 0.64-1.00; P = .055), and locoregional recurrence (RR, 0.76; 95% CI, 0.53-1.08; P = .127). There were no significant differences between treatment with extended AIs and control for grade 3 or more adverse events.ConclusionExtended AI therapy could significantly improve DFS, especially for contralateral breast cancer recurrence. There were no significant differences between treatment with AIs and control for OS, distant metastatic and locoregional recurrence, and serious adverse events.     

Neoadjuvant Sunitinib Decreases Inferior Vena Caval Thrombus Size and Is Associated With Improved Oncologic Outcomes: A Multicenter Comparative Analysis

BackgroundWe analyzed outcomes of neoadjuvant sunitinib in patients with renal-cell carcinoma (RCC) and inferior vena caval (IVC) tumor and compared outcomes to patients who did not undergo neoadjuvant therapy before surgery.Patients and MethodsWe performed a multicenter retrospective comparison of RCC patients with IVC tumor who underwent neoadjuvant sunitinib before surgery versus those who did not. Response to sunitinib was defined by Response Evaluation Criteria in Solid Tumors (RECIST). Primary outcome was cancer-specific survival. Secondary outcomes included overall survival. Multivariate analysis was performed to identify risk factors associated with primary and secondary outcomes. Kaplan-Meier analysis compared survival in neoadjuvant and primary surgery groups.ResultsData of 53 patients were analyzed (19 neoadjuvant sunitinib, 34 primary surgery; median follow-up, 58 months). Eighteen (9 in each group, P = .143) had metastatic RCC. There was no difference in IVC tumor level between the 2 groups (P = .76). After neoadjuvant sunitinib, median primary tumor decreased size from 8.1 to 6.8 cm, and IVC tumor decreased by 1.3 cm. IVC tumor level decreased in 8 (42.1%) of 19 and was stable in 10 (52.6%) of 19; 5 (26.3%) of 19 experienced partial response. Similar proportions of patients underwent robot-assisted or minimally invasive approaches (P = .351), and no differences were noted in complications (P = .194). Multivariate analysis showed neoadjuvant sunitinib was associated with improved cancer-specific survival (odds ratio = 3.28; P = .021). Kaplan-Meier analysis demonstrated significantly longer median cancer-specific survival (72 vs. 38 months, P = .023) for neoadjuvant sunitinib.ConclusionNeoadjuvant sunitinib was associated with a reduction in primary tumor and thrombus size as well as improved survival. Further investigation is needed to determine the utility of neoadjuvant sunitinib in RCC with IVC tumor.     

Survival of women with inflammatory breast cancer: a large population-based study

BackgroundOur group has previously reported that women with inflammatory breast cancer (IBC) continue to have worse outcome compared with those with non-IBC. We undertook this population-based study to see if there have been improvements in survival among women with stage III IBC, over time.Patient and methodsWe searched the Surveillance, Epidemiology and End Results Registry to identify female patients diagnosed with stage III IBC between 1990 and 2010. Patients were divided into four groups according to year of diagnosis: 1990–1995, 1996–2000, 2001–2005, and 2006–2010. Breast cancer-specific survival (BCSS) was estimated using the Kaplan–Meier method and compared across groups using the log-rank test. Cox models were then fit to determine the association of year of diagnosis and BCSS after adjusting for patient and tumor characteristics.ResultsA total of 7679 patients with IBC were identified of whom 1084 patients (14.1%) were diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000, 2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between 2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were 62%, 67%, 72%, and 76% for patients diagnosed between 1990–1995, 1996–2000, 2001–2005, and 2006–2010, respectively (P < 0.0001). In the multivariable analysis, increasing year of diagnosis (modeled as a continuous variable) was associated with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence interval 0.97–0.99, P < 0.0001).ConclusionThere has been a significant improvement in survival of patients diagnosed with IBC over a two-decade time span in this large population-based study. This suggests that therapeutic strategies researched and evolved in the context of non-IBC have also had a positive impact in women with IBC.     

Clinicopathologic Implications of EpCAM and Sox2 Expression in Breast Cancer

BackgroundThe purpose of this study was to investigate the clinicopathologic significance of EpCAM and Sox2 expression in breast cancer and to study their correlation during breast cancer progression.Patients and MethodsEpCAm and Sox2 expression were assessed using immunohistochemistry in ductal carcinoma insitu (DCIS), invasive breast cancer (IBC) and matched lymph node metastasis (LNM), if present.ResultsEpCAM overexpression was found in 63.2% of DCIS, 72.2% of IBC and 74.4% of LNM. In IBC cases, EpCAM overexpression was associated with high grade (P < .001), large tumor size (P = .051), poor Nottingham Prognostic Index (NPI) (P = .006), histological tumor types (P = .044) and the triple negative phenotype (P = .008). LNM frequently reflected the expression phenotype of the matched primary tumors with no significant differences between LNM and their primary tumors (P = .564). Sox2 expression was detected in 47.4%, 33.3% and 54.7% of DCIS, IBC and LNM respectively. In DCIS group, Sox2 expression was significantly associated with comedo type (P = .037), negative ER (P = .012) and PR (P = .037) and the triple negative phenotype (P = .006). In IBC cases, Sox2 expression showed significant associations with high grade (P = .045), nodal spread (P = .037), poor NPI (P = .018) and the triple negative phenotype (P < .001). LNM showed significantly higher Sox2 expression rates than primary tumors (P < .001). Significant positive associations between EpCAM overexpression and Sox2 positivity in DCIS (P = .027), IBC (P = .001) and LNM (P < .001) were found.ConclusionThis study emphasized the potential role of EpCAM and Sox2 in breast carcinogenesis and revealed their involvement during breast cancer progression and LN metastases.     

Patterns of locoregional failure in women with early-stage breast cancer treated by whole breast irradiation in the lateral isocentric decubitus position: Large-scale single-centre experience

PurposeThe purpose of this study was to evaluate locoregional control and describe the patterns of failure in patients with breast cancer receiving whole breast radiotherapy in the isocentric lateral decubitus position technique.Patients and methodsIn a series of 832 consecutive female patients with early-stage breast cancer including invasive and in situ tumours treated by breast-conserving surgery followed by three-dimensional conformal whole breast irradiation in the isocentric lateral decubitus position between 2005 and 2010, all patients who experienced locoregional recurrence were studied. Five-year recurrence-free and overall survival rates were calculated. Regional recurrence mapping patterns were also determined.ResultsThe median age of this series of 832 women was 61.5 years (range: 29–90 years). Various types of fractionation were used: 50 Gy in 25 fractions (17.9%), 66 Gy in 33 fractions (50 Gy in 25 fractions to breast followed by sequential boost to tumour bed to a total dose 66 Gy in 33 fractions.) (46.5%), 40 Gy in 15 fractions or 41.6 Gy in 13 fractions (26.1%) and 30 Gy in 5 fractions (9.5%). With a median follow-up of 6.4 years, only 36 patients experienced locoregional recurrence and no association with the fractionation regimen was identified (P = 0.2). In this population of 36 patients, 28 (3.3%) had “in-breast” local recurrences (77.8%), two had local recurrences and regional lymph node recurrence (5.6%), and six had regional lymph node recurrence only (in non-irradiated areas; 16.6%). The median time to recurrence was 50 months. Complete mapping of patterns of recurrences was performed and, in most cases, local recurrences were situated adjacent to the primary tumour bed. Cases of local recurrences presented a significantly lower distant metastasis rate (P < 0.001) and had a significantly longer overall survival compared to patients with regional lymph node recurrence (P < 0.001). However, multivariate Cox regression analysis showed that the site of recurrence had no significant impact on overall survival (P = 0.14).ConclusionThe results of this study indicate a low local recurrence rate. Further careful follow-up and recording of recurrences is needed to improve the understanding of patterns of recurrence.     

Valeur pronostique des sous-types moléculaires et du Ki67 pour les cancers du sein indemnes d’envahissement ganglionnaire après mastectomie : expérience de l’institut Curie–hôpital René-Huguenin et revue de la littérature

PurposeTo evaluate the prognostic value of Ki67 expression, breast cancer molecular subtypes and the impact of postmastectomy radiotherapy in breast cancer patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy.Patients and methodsSix hundred and ninety-nine breast cancer patients with pN0 status after modified radical mastectomy, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumours were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of locoregional recurrence associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors.ResultsAt a median follow-up of 56 months, 17 patients developed locoregional recurrence. Five-year locoregional recurrence-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the postmastectomy radiotherapy (n = 191) and no-postmastectomy radiotherapy (n = 508) subgroups. No constructed subtype was associated with an increased risk of locoregional recurrence. A Ki67 above 20% was the only independent prognostic factor associated with increased locoregional recurrence (hazard ratio, 4.18; 95% CI, 1.11 to 15.77; P < 0.0215). However, postmastectomy radiotherapy was not associated with better locoregional control in patients with proliferative tumours.ConclusionKi67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after modified radical mastectomy. The benefit of adjuvant radiotherapy in patients with proliferative tumours should be further investigated in prospective studies.     

Disseminated tumor cells and the risk of locoregional recurrence in nonmetastatic breast cancer

BackgroundIn early breast cancer patients, bone marrow (BM)-disseminated tumor cells (DTCs) were associated with distant metastasis and locoregional recurrence. Our aim was to determine whether BM DTC detection could be related to specific locoregional dissemination of cancer cells, according to radiotherapy volumes.Patients and methodsThe relationship between locoregional recurrence-free survival (LRFS) and DTC detection was evaluated according to the various locoregional volumes irradiated after surgery.ResultsBM DTCs were detected in 94 of 621 stage I–III breast cancer patients (15%) and were not associated with axillary node status. Eighteen patients (2.9%) experienced locoregional recurrence (median follow-up 56 months), of whom eight (44%) were initially BM DTC positive. BM DTC detection was the only prognostic factor for LRFS [P = 0.0005, odds ratio = 5.2 (2.0–13.1), multivariate analysis]. In BM DTC-positive patients, a longer LRFS was observed in those who were given adjuvant hormone therapy (P = 0.03) and radiotherapy to supraclavicular nodes (SCNs)/internal mammary nodes (IMNs) (P = 0.055) (multivariate analysis; interaction test: P = 0.028).ConclusionsThe presence of DTC in BM may be associated with a different pattern of locoregional cancer cell dissemination and influences LRFS. The possible reseeding of the primary cancer area by DTC could be prevented by systemic hormone therapy but also by SCN/IMN irradiation.