Aggressive Treatment for Hepatic Metastases from Breast Cancer: Results from a Single Center

Background

Breast cancer (BC) is the most common cancer among women worldwide. It has been estimated that approximately 12–20 % of patients will develop liver metastases from breast cancer (BCLM) and that in approximately 5 % of cases the liver is the only metastatic site. Patients with isolated BCLM have the poorest prognosis with a median survival ranging from 19 to 26 months.

Methods

A total of 26 women with isolated BCLM and without any sign of disease progression after a cycle of chemotherapy were retrospectively reviewed. Women were treated with hepatic resection (HR) for unilobar disease or surgical “open” RFA for bilobar disease. Data were collected on either original BC or BCLM and from patients follow-up.

Results

Overall survival from BC diagnosis was 47.69 ± 22.25 months (range 33–84, median 45.5 months); it was 52.25 ± 14.57 months (range 33–84, median 48.5 months) for the HR patients and 43.79 ± 27.14 months (range 9–101, median 39 months) for the RFA patients. Overall survival from BCLM treatment was 21.12 ± 12.78 months (range 9–64, median 15.5 months); in detail it was 29.42 ± 14.53 months (range 12–64, median 29.5 months) for the resected patients and 14 ± 4.45 months (range 9–24, median 13.5 months) for patients treated by RFA with a strongly significant survival difference for operated patients (p = 0.001). Overall disease-free survival from BCLM was 15.96 ± 13.16 months (range 3–64, median 12 months), disease-free survival for resected patients was 23.22 ± 16.2 months (range 8–64, median 18.5 months), and for patients treated by RFA was 9.64 ± 4.22 months (range 3–18, median 9 months; Fig. 1). Overall 1, 2, and 5 years (actuarial) survival was respectively 80.7, 57, and 31 %. Given in details for the two groups, they were respectively 100, 66.6 and 34 % (actuarial) for the resected group patients and 64.2, 21.4, and 11.5 % (actuarial) for the RFA patients.

Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy

BackgroundFive to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation.Patients and methodsRetrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation.ResultsSeventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary (“de novo/surgery”). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with “recurring”, “de novo/surgery” and “de novo” without surgery (“de novo/no surgery) stage IV breast cancer. However, women with “de novo/surgery” stage IV breast cancer had the longest median OS (60 months), and those with “de novo/no surgery” stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings.ConclusionOur analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias.     

Surgical Treatment of Extrapulmonary Oligometastatic Non-small Cell Lung Cancer

The prognosis of metastatic non-small cell lung cancer (NSCLC) is poor, and platinum-based chemotherapy improves the median survival for only a few months. A subgroup of patients with oligometastatic disease may benefit from surgical resection, but only very limited data are available to date. We conducted a retrospective review of all patients with synchronous extrapulmonary oligometastatic NSCLC undergoing surgical resection in our department. Data regarding medical history, histology, number of metastases, and survival status were extracted from the medical database of the University Medical Center, Freiburg. Fifty-six patients underwent surgical resection for oligometastatic lung cancer. Five patients were lost during follow-up and therefore censored. One patient died perioperatively due to acute respiratory distress syndrome. The remaining 50 patients had an overall median survival time of 14.6 months. Analyzing the influence of metastatic site, we found a median overall survival of 23.4 months for patients with soft tissue metastasis, 16.7 months for patients with brain metastasis, 9.5 months for patients with adrenal gland involvement, and only 4.3 months for patients with bone metastasis (p?<?0.005). Upon multivariate analysis, bone metastasis was the only significant parameter influencing median overall survival (p?<?0.004). Based on our data, we conclude that an aggressive surgical approach for oligometastatic NSCLC can be performed with acceptable mortality and morbidity. In this rare constellation, surgical therapy may be an option in selected cases.     

Revisiting the Concept of Lymph Node Metastases of Pancreatic Head Cancer: Number of Metastatic Lymph Nodes and Lymph Node Ratio According to N Stage

Background

Some suggest that metastatic lymph node ratio (LNR) may be prognostic of survival in patients with pancreatic cancer. However, this phenomenon was confused by inclusion of node-negative patients in the analysis. The present study was designed to evaluate the prognostic impact of metastatic LNR and the absolute number of metastatic LNs in patients resected for pancreatic cancer.

Methods

Data were collected from 398 patients who underwent curative surgery for pancreatic head cancer at Seoul National University Hospital. Long-term survival was analyzed according to LNR and absolute number of metastatic LNs.

Results

Of the patients, 227 (57.0 %) had LN metastasis. The mean numbers of total retrieved and metastatic LNs were 19.5 and 1.9, respectively, and the mean LNR was 0.11. Median overall survival (OS) of patients was significantly higher in N0 than in N1 patients after curative resection (25.4 vs. 14.8 months, p < 0.001). Median OS was significantly lower in patients with 1 than in those with 0 positive LNs (17.3 vs. 25.4 months, p = 0.001). Among N1 patients, those with 0 < LNR ≤ 0.2 had comparable prognosis than those with >0.2 LNR (median OS 17.2 vs. 12.8 months, p = 0.096), and the number of metastatic LNs did not correlate with median OS (p = 0.365).

Conclusions

The presence of a single positive metastatic LN was associated with significantly poorer OS in patients with pancreatic cancer. When LN metastasis was present, the number of metastatic LNs and LNR had limited prognostic relevance.     

Breast cancer subtypes and outcomes of central nervous system metastases

Central nervous system (CNS) metastases are detected in up to one third of patients with advanced breast cancer, but their incidence and outcomes by breast cancer subtypes are not precisely documented. Herein, we retrospectively analyzed clinicopathologic data of 259 breast cancer patients with CNS metastases to evaluate the association between breast cancer subtypes and CNS metastasis. The patient groups were classified according to their hormone receptor status and HER-2 expression. Median follow-up time among the patients was 42 months and median survival after CNS metastasis detection was 7.8 months. In HER-2 overexpressing group, median time period between the diagnosis of breast cancer and the detection of CNS metastasis (15.9 months) was significantly shorter compared to the other groups (p = 0.01). The triple negative group had the shortest median survival time after CNS metastasis (6.6 months), although statistically not significant (p = 0.3). In multivariate Cox regression analyses, having solitary CNS metastasis (HR 0.4, 95% CI; 0.2–0.7, p = 0.004), and receiving chemotherapy after CNS metastasis (HR 0.4, 95% CI; 0.287–0.772, p = 0.003) were independent prognostic factors for increasing survival after CNS metastasis. In conclusion, new and effective treatment strategies are required for breast carcinoma patients with brain metastasis considering the positive effect of the treatment on survival.     

Clinical outcomes and treatment practice patterns of patients with HER2-positive metastatic breast cancer in the post-trastuzumab era

BackgroundTrastuzumab is associated with improvements in overall survival (OS) among patients with HER2-positive metastatic breast cancer (MBC); however disease course and patterns of care in individual patients are highly variable.Methods113 HER2-positive patients diagnosed with MBC from 1999 to 2005 who received trastuzumab-based therapy were retrospectively identified to allow for a minimum of 5 years of follow-up time. Median OS and median duration of therapy were determined using Kaplan–Meier methodology and group comparisons were based on the log-rank test. Hazard ratios (HR) were obtained using a Cox proportional hazards model.ResultsMedian OS was 3.5 years (95% CI 3.0–4.4) from time of initiation of first therapy in the metastatic setting. On univariate analysis, central nervous system (CNS) disease at first recurrence was associated with a shorter OS compared with liver and/or lung metastases or other sites (CNS: 1.9 years CI 0.1–5.9, liver/lung: 3.2 years CI 2.5–4.2, other: 4.6 years CI 2.7–8.0; p = 0.05), however, this was not predictive of survival outcome in multivariate analysis. CNS metastases developed in 62 (55%) patients by the time of death or last follow-up. Median duration of therapy was similar up to 6 lines of treatment, and ranged from 5.2 months to 7.2 months.ConclusionsThe natural history of HER2-positive MBC has evolved with trastuzumab-based therapy with median OS now exceeding 3 years. CNS disease is a major problem with continued risk of CNS progression over time. Patients demonstrate clinical benefit to multiple lines of HER2-directed therapy.     

Outcome and Prognostic Factors After Adrenalectomy for Patients with Distant Adrenal Metastasis

Background

The purpose of this study was to describe a single-institution experience with adrenal metastasectomy and to elucidate factors that may bear prognostic significance.

Methods

This is a single-center, retrospective review of patients with adrenal metastasis who underwent adrenalectomy performed with curative intent between 2000 and 2012. The Kaplan–Meier method was used to evaluate overall survival from time of adrenalectomy to death or last follow-up. Primary endpoint was death from any cause. Clinical variables were examined for association with survival.

Results

The study included 62 patients with mean age of 60 (±12) years; 55 % (34 of 62) were male, 85 % (53 of 62) presented with isolated adrenal metastasis, and 82 % (51 of 62) had metachronous disease with median disease-free interval (DFI) of 22 months (range, 6–217 months). Non-small cell lung cancer (NSCLC) was the most common primary comprising 50 % of cases. Median survival for the study population was 30 months (range, 1–145 months) and 5-year survival was 31 %. Patients with NSCLC had significantly shortened survival compared with non-NSCLC with median and 5-year survival of 17 versus 47 months and 27 % versus 38 %, respectively (p = .033). Synchronous metastasis (p = .028) and DFI < 12 months (p = .038) were also associated with worse survival outcome, though male gender (p = .69) and oligometastatic disease (p = .62) were not.

Conclusions

Adrenal metastasectomy resulted in median survival of 30 months and 5-year survival of 31 %. Shorter survival was associated with lung primary, short disease-free interval, and synchronous metastasis, but not with the presence of oligometastatic disease provided that the primary cancer and additional metastatic lesions were adequately controlled and amenable to resection.     

Prognosis in Women with Breast Cancer and Private Extra Insurance Coverage

Background

Many women covered by the Spanish public health system also have an extra private insurance policy for gynecological examinations and routine annual mammography. We retrospectively analyzed the long-term survival rates in these patients when diagnosed with breast cancer.

Methods

We analyzed the survival and prognostic factors in patients diagnosed with breast cancer who were referred to a medical oncology unit for multidisciplinary treatment covered by private health insurance.

Results

Between 1994 and 2009, a total of 434 patients with breast tumor were analyzed: 33 in situ and 401 infiltrating. Among the infiltrating carcinomas, 38 were stage IV and 363 were stage I, II, or III. With a median follow-up of 62 months, the 5-year global survival rate was 91 %: 97 % for stage I, 94 % for stage II, and 77 % for stage III tumors. In the patients diagnosed by routine mammography, the 5-year survival rate was 96 %, compared with 86 % in those consulting their gynecologist after breast self-examination or for other symptoms (p = 0.0159). Seventy-four percent were treated conservatively and experienced better survival than the 26 % who underwent mastectomy (p = 0.0024). Patients with disease with positive hormone receptors had a better survival rate (p = 0.0264); hormone receptor status was the only independent prognostic factor in the Cox multivariate analysis. Postmenopausal patients who received adjuvant tamoxifen plus exemestane had a better prognosis than those who received tamoxifen alone (p = 0.0203).

Conclusions

Long-term survival rate was high in breast cancer patients with extra private insurance coverage. This is probably because disease was diagnosed at an early stage.     

Failure of Normalization of CA19-9 Following Resection for Pancreatic Cancer is Tantamount to Metastatic Disease

Background

Multidisciplinary therapy for pancreatic cancer involves radical resection followed by gemcitabine-based chemotherapy. Carbohydrate antigen 19-9 (CA19-9), when elevated preoperatively, is a useful marker to monitor disease status following resection. However, little has been reported on outcomes of patients in whom CA19-9 never normalizes. We hypothesize that failure of CA19-9 normalization within 6 months is prognostically equivalent to metastatic disease.

Methods

From our pancreatectomy database, we identified 93 patients with pancreatic adenocarcinoma and elevated CA19-9 prior to resection with levels recorded postoperatively. Patients were grouped based on normalization or persistent elevation of CA19-9 at 6 months after resection. CA19-9 levels normalized (≤35 u/ml) after resection in 38 (41%) and remained elevated in 55 (59%). Clinicopathologic characteristics were compared using Student’s t-test and contingency table analyses. Survival curves were constructed using Kaplan–Meier method and compared by log-rank analysis. Cox regression was used to determine predictors of survival.

Results

The two groups had comparable clinicopathologic characteristics except for nodal status and perineural invasion, which were higher in patients with persistently elevated CA19-9. Persistent CA19-9 conferred shorter median overall survival of 10.8 months compared with 23.8 months in patients with normalization (p < 0.001), which persisted when controlling for nodal status. Multivariate analysis demonstrated persistently elevated CA19-9 as the sole statistically significant negative predictor of survival [hazard ratio (HR) 2.20, p = 0.002].

Conclusions

Persistent CA19-9 elevation after pancreatectomy correlates with shorter survival analogous to unresected or metastatic disease and should be regarded as persistent disease regardless of radiographic findings. These patients should be considered for accrual to clinical trials or initiation of alternative therapy.     

Endoscopic and Pathologic Findings Associated with Clinical Outcomes of Melanoma in the Upper Gastrointestinal Tract

Background

Melanoma that involves the upper gastrointestinal (GI) tract is rare and studies relating to endoscopic and pathologic findings with clinical outcomes are lacking. We reviewed the gross and microscopic patterns of the upper GI tract in primary and metastatic melanoma, and examined their association with clinical outcomes.

Methods

Twenty-nine cases of primary esophageal (n = 19) and metastatic gastric and/or duodenal melanoma (n = 10) that were detected during upper GI endoscopy between 1995 and 2011 were retrospectively analyzed.

Results

Three types of gross patterns were recognized—nodular pattern in 7 cases, mass-forming pattern in 18 cases, and flat pigmented pattern in 4 cases. In primary esophageal melanoma, 13 patients (68.4 %) underwent surgery and 9 received palliative therapy. Of all cases, 22 patients (75.9 %) died of disease progression; the median overall survival period was 12 months (interquartile range [IQR] 4.5–24.5 months), and from recognition of upper GI tract melanoma the median overall survival period was 9 months (IQR 3.5–17.0 months). In primary esophageal cases, skin melanoma stage better discriminated the patients with good prognosis than the esophageal cancer stage. The flat pigmented gross pattern proved to be a good prognostic factor in primary and metastatic GI tract melanomas (p = 0.016 and p = 0.046, respectively).

Conclusions

Melanoma of the GI tract is a highly aggressive disease with a poor prognosis, both in primary and metastatic cases. However, in primary esophageal melanoma, careful inspection of the mucosa during endoscopic examination followed by surgical resection may result in extended survival.     

Surgical Resection of the Primary Tumor is Associated with Increased Long-Term Survival in Patients with Stage IV Breast Cancer after Controlling for Site of Metastasis

Background The benefit of surgical resection in patients presenting with metastatic breast cancer is not established. We hypothesized that surgical excision of primary tumors in patients with stage IV breast cancer would be associated with increased survival. Methods Chart review identified 409 patients with stage IV breast cancer treated from 1996 to 2005; 187 received surgical excision of their primary tumor and 222 did not. One hundred and two patients had bone-only metastases, 281 had metastases to other organs ± bone, and 26 had no metastases recorded. Patient characteristics were compared between groups using the chi-squared test. Cox regression models were used to calculate adjusted hazard ratios (aHR). The log-rank test compared the differences in survival between patients who did or did not undergo surgical resection. Results Mean age at diagnosis of all 409 patients was 57.8 ± 15.0 years. After controlling for age, comorbidity, tumor grade, histology, and sites of metastasis, patients who underwent surgical resection had longer median survival when compared with patients who did not undergo surgical resection (31.9 vs. 15.4 months, p < 0.0001; aHR 0.53 [95% CI 0.42-0.67]). Conclusions Surgical excision of the primary breast tumor was associated with significantly longer survival in this cohort of stage IV breast cancer patients, even after controlling for other factors associated with survival. Randomized clinical trials are needed to validate these findings.     

Hepatic metastases from breast cancer

The prognosis of patients with hepatic metastasis from breast cancer treated with systemic or regional chemotherapy is disappointing. When technically feasible, liver resection offers the best results. Eighteen patients out of 22 submitted to laparotomy underwent radical liver resection. Median follow-up from liver resection was 36 months. The median time interval between breast cancer diagnosis and disease recurrence was 35 months. Median disease-free survival and overall survival from liver resection were 66 and 74 months, respectively. Median survival time from breast cancer surgery was 88.5 months. Surgical treatment of liver metastases should be carried out on young and older patients alike when site of metastases is the liver alone. Neoadjuvant treatment and preoperative diagnostic laparoscopy should be planned in future experience.     

Re-resection for Isolated Local Recurrence of Pancreatic Cancer is Feasible, Safe, and Associated with Encouraging Survival

Background

Local recurrence of pancreatic cancer occurs in 80 % of patients within 2 years after potentially curative resections. Around 30 % of patients have isolated local recurrence (ILR) without evidence of metastases. In spite of localized disease these patients usually only receive palliative chemotherapy and have a short survival.

Purpose

To evaluate the outcome of surgery as part of a multimodal treatment for ILR of pancreatic cancer.

Methods

All consecutive operations performed for suspected ILR in our institution between October 2001 and October 2009 were identified from a prospective database. Perioperative outcome, survival, and prognostic parameters were assessed.

Results

Of 97 patients with histologically proven recurrence, 57 (59 %) had ILR. In 40 (41 %) patients surgical exploration revealed metastases distant to the local recurrence. Resection was performed in 41 (72 %) patients with ILR, while 16 (28 %) ILR were locally unresectable. Morbidity and mortality were 25 and 1.8 % after resections and 10 and 0 % after explorations, respectively. Median postoperative survival was 16.4 months in ILR versus 9.4 months in metastatic disease (p < 0.0001). In ILR median survival was significantly longer after resection (26.0 months) compared with exploration without resection (10.8 months, p = 0.0104). R0 resection was achieved in 18 patients and resulted in 30.5 months median survival. Presence of metastases, incomplete resection, and high preoperative CA 19-9 serum values were associated with lesser survival.

Conclusions

Resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with favorable survival outcome. This concept warrants further evaluation in other institutions and in randomized controlled trials.     

Meta-Analysis to Determine if Surgical Resection of the Primary Tumour in the Setting of Stage IV Breast Cancer Impacts on Survival

Introduction

The role of primary tumor excision in patients with stage IV breast cancer is unclear. Therefore, a meta-analysis of relevant studies was performed to determine whether surgical excision of the primary tumor enhances oncological outcome in the setting of stage IV breast cancer.

Methods

A comprehensive search for relevant published trials that evaluated outcomes following excision of the primary tumor in stage IV breast cancer was performed using MEDLINE and available data were cross-referenced. Data were extracted following review of appropriate studies by authors. The primary outcome was overall survival following surgical removal of the primary tumor.

Results

Data from ten studies included 28,693 patients with stage IV disease of whom 52.8 % underwent excision of the primary carcinoma. Surgical excision of the primary tumor in the setting of stage IV breast cancer was associated with a superior survival at 3 years (40 % (surgery) versus 22 % (no surgery) (odds ratio 2.32, 95 % confidence interval 2.08–2.6, p < 0.01). Subgroup analyses for selection of patients for surgery or not, favored smaller primary tumors, less competing medical comorbidities and lower metastatic burden (p < 0.01). There was no statistical difference between the two groups regarding location of metastatic disease, grade of tumor, or receptor status.

Conclusions

Patients with stage IV disease undergoing surgical excision of the primary tumor achieve a superior survival rate then their nonsurgical counterparts. In the absence of robust evidence, this meta-analysis provides evidence base for primary resection in the setting of stage IV breast cancer for appropriately selected patients.     

Reconstruction in the Metastatic Breast Cancer Patient: Results from the National Cancer Database

Purpose

Modern treatments are prolonging life for metastatic breast cancer patients. Reconstruction in these patients is controversial. The purpose of this study was to characterize de novo metastatic breast cancer patients who undergo mastectomy and reconstruction and to report complication and survival rates.

Methods

We queried the National Cancer Database for de novo metastatic breast cancer patients, who underwent systemic therapy and mastectomy with reconstruction (R) or without reconstruction (NR) between 2004 and 2013. Patient-tumor characteristics, mortality, and readmissions were compared. Propensity score matched analysis was performed, and survival was calculated using the Kaplan–Meier method.

Results

A total of 8554 patients fulfilled study criteria (n?=?980/11.5% R vs. n?=?7574/88.5% NR). There was a significant increase in reconstruction rates by year: 5.2% in 2004, 14.3% in 2013 (p?<?0.0001). Compared with the NR patients, R patients were younger (mean age 49 vs. 58 years, p?<?0.0001), more hormone receptor-positive (76.1% vs. 70.5%, p?=?0.0004), had lower grade disease (p?=?0.0082), and fewer sites of metastases (85.7% had 1 metastasis; 14.3% had?≥?2 R vs. 79% had 1; 21% had?≥?2 NR, p?=?0.0002). R patients received more hormonal and chemotherapy than NR but equally received radiation. Median overall survival of the total cohort was 45 months, and median overall survivals of R and NR groups by matched analysis were 56.7 and 55.3 months respectively (p?=?0.86). Thirty-day mortality (0.2%-R, 0.3%-NR, p?=?0.56) and readmissions (5.9%-R, 5.8%-NR, p?=?0.81) were similar; 90-day mortality also was similar (1.1%-R vs. 1.6%-NR, p?=?0.796).

Conclusions

There is an increasing trend to reconstruct metastatic breast cancer patients with low complication rates, without survival compromise. Impact on quality of life warrants further assessment.

     

Higher Rate of Breast Surgery Complications in Patients with Metastatic Breast Cancer: An Analysis of the NSQIP Database

Background

Four percent of breast cancer patients present with metastatic disease. To date, no one has examined whether these patients are at higher risk of postoperative complications. The objective of this study was to determine morbidity and mortality associated with breast surgery in the metastatic setting.

Methods

We analyzed the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, including breast cancer patients undergoing primary breast surgery from 2005 to 2012. Patients with bilateral surgery or severe comorbidities were excluded. Multivariable logistic regression was performed to determine the independent effect of metastatic breast cancer on postoperative morbidity and mortality.

Results

We identified 68,316 patients who underwent breast surgery for invasive breast cancer; 1,031 (1.5 %) had metastatic disease. The 30-day unadjusted morbidity was significantly higher in the metastatic cohort (7.5 vs. 3.7 %; p < 0.001), as was the all-cause 30-day mortality (1.8 vs. 0.06 %; p < 0.001). The metastatic cohort was more likely to experience an: infectious, respiratory, thromboembolic, cardiac, or bleeding complication than non-metastatic patients. However, preoperative chemo- and radiation therapy did not contribute to an overall increased complication rate. The adjusted odds ratio for postoperative complications in the setting of metastatic disease was 1.6 (95 % confidence limit 1.2–2.1).

Conclusions

This is the first study documenting the morbidity and mortality associated with breast surgery in metastatic breast cancer. The 30-day morbidity and mortality in this population is higher than in patients with stage I–III disease. Although the complication rate is increased, operating on the primary in metastatic breast cancer is relatively safe.     

Long-Term Outcome of Neoadjuvant Endocrine Therapy with Aromatase Inhibitors in Elderly Women with Hormone Receptor-Positive Breast Cancer

Background

Aromatase inhibitors (AIs) are more effective than tamoxifen as neoadjuvant endocrine therapy (NET) for hormone receptor (HR)-positive breast cancer. Here we report the surgical and long-term outcome of elderly postmenopausal patients with locally advanced, HR-positive breast cancer treated with preoperative AIs.

Methods

Between January 2003 and December 2012, 144 postmenopausal patients inoperable with breast conservative surgery (BCS) received letrozole, anastrozole, or exemestane as NET. Patients underwent breast surgery and received adjuvant AIs. Adjuvant systemic therapy, chemotherapy and/or trastuzumab, and adjuvant radiotherapy were administered as appropriate, but limited to high-risk patients with few or no comorbidities.

Results

After a median follow-up of 49 months, 4 (3.0 %) patients had local relapse, 18 (12.5 %) had distant metastases, and 24 (17.0 %) died. BCS was performed in 121 (84.0 %) patients. A tumor size <3 cm and human epidermal growth factor receptor 2 (HER2) negativity were predictors of BCS. The achievement of BCS and grade G1 were significantly associated with longer disease-free survival (DFS) (p = 0.009 and p = 0.01, respectively) and overall survival (p = 0.002 and p = 0.005, respectively). Residual tumor ≤2 cm (yT0–yT1) in the longest diameter after NET was also statistically associated with longer DFS (p = 0.005).

Conclusions

The results of this retrospective study indicate that elderly breast cancer patients with a tumor size <3 cm at diagnosis and HER2 negativity have a higher probability of achieving BCS after NET. Moreover, patients treated with BCS and with grade G1 tumor have a reduced risk of recurrence and death in the long-term follow-up.     

Clinicopathological features and treatment outcomes of metastatic tumors in the stomach

The metastasis of tumors to the stomach is rare, which underlies the clinical problems regarding their diagnosis and treatment. The present review summarizes the current knowledge regarding the clinicopathological characteristics, therapeutic strategies and outcomes for metastatic tumors in the stomach. The primary malignancies of the metastatic tumors in the stomach were most often breast cancers (27.9 %), followed by lung cancer (23.8 %), esophageal cancer (19.1 %), renal cell carcinoma (RCC; 7.6 %) and malignant melanoma (7.0 %). In cases of breast cancer and RCC as the primary malignancy, the median interval between the treatment of the primary tumor and diagnosis of the metastatic tumor in the stomach (IPM) was 50–78 and 75.6 months, respectively, highlighting the fact that the metastatic spread to the stomach may occur many years after the initial treatment of the cancer. In nine patients with metastatic gastric tumors arising from ovarian cancer, an endoscopic examination revealed submucosal tumors in six patients (66.7 %), with a median IPM of 30 months. Appropriate systemic treatment for these tumors is the preferred therapeutic strategy. Although solitary metachronous gastric metastasis several years after treatment of the primary tumor is an exceptionally rare event, surgical resection of metastatic gastric tumors may be recommended to control hemorrhaging or for selected tumors.     

Co-overexpression of HER2/HER3 is a predictor of impaired survival in breast cancer patients

BackgroundRecently, HER3-expression was postulated as independent risk factor for metastatic spread. Therefore, we investigated the role of HER3 expression as prognostic marker in metastatic breast cancer patients.MethodsPatients of different breast cancer subtypes diagnosed with metastatic disease (visceral and/or brain metastases) were identified from a breast cancer database. Tissue samples of the respective primary tumors were retrieved, and immunohistochemical staining for estrogen-receptor, progesterone-receptor, HER2, and HER3 was performed. In HER2 equivocal and selected HER3 positive cases, subsequent fluorescent in situ hybridization (FISH) analysis was performed.ResultsTissue specimens of 110 patients were available for this analysis. 21% had strong, complete, membranous HER3 staining of at least 10% of all tumor cells; HER3 protein expression was not associated with HER3 gene amplification. HER2/HER3 co-overexpression was observed in 12/110 (11%) specimens and HER3-overexpression showed a statistically significant association with HER2-overexpression (p = 0.02). No correlation was observed for HER3-overexpression and overall survival (OS), time to diagnosis of brain metastases, and incidence of brain metastases. Still, in patients with HER3 overexpression, a higher rate of ‘brain only’ metastatic behavior was observed (p = 0.042). In the HER2-positive subgroup, HER3-overexpression was significantly associated with shorter OS from diagnosis of metastatic disease (median 17 vs. 35 months; p = 0.04; log rank test).ConclusionsHER2/HER3 co-overexpression is significantly associated with impaired OS from diagnosis of metastatic disease in patients with HER2-positive metastatic breast cancer. Co-inhibition of HER2 and HER3 or the inhibition of HER2/HER3 hetero-dimerization may improve clinical outcome in this subgroup.     

Female sex is an independent risk factor for reduced overall survival in bladder cancer patients treated by transurethral resection and radio- or radiochemotherapy

Purpose

To evaluate sex as a possible prognostic factor in bladder cancer patients treated with transurethral resection (TURBT) and radio- (RT) or radiochemotherapy (RCT).

Methods

Kaplan–Meier analyses and multiple Cox proportional hazards regression analyses were performed to analyze sex as a possible prognostic factor on the overall (OS) and cancer-specific (CSS) survival of 386 male and 105 female patients who underwent TURBT and RCT or RT with curative intent between 1982 and 2007.

Results

After a follow-up of 5 years, female sex demonstrated a hazard ratio (HR) of 1.79 (95 % CI 1.24–2.57) for OS; for CSS, the HR was 2.4 (95 % CI 1.52–3.80). Sex was an adverse prognosticator of both OS and CSS independent from age at diagnosis, cT stage, grading, concurrent cis, LVI, focality, therapy response, resection status and therapy mode. Kaplan–Meier analysis showed significantly reduced OS of women compared with men, with a median survival of 2.3 years for female patients and 5.1 years for male patients (p = 0.045, log-rank test). The estimated median CSS was 7.1 years for female patients and 12.7 years for male patients (p = 0.11, log-rank test).

Conclusions

Female sex is an independent prognostic factor for reduced OS and CSS in bladder cancer patients treated by TURBT and RT or RCT. These data are in agreement with those reported for OS after radical cystectomy in muscle-invasive bladder cancers. Therefore, further studies are strongly warranted to obtain more information about molecular differences regarding sex-specific carcinogenesis in bladder cancer and about possible therapeutic considerations.