Survival Outcomes of Different Treatment Methods for the Ipsilateral Breast of Occult Breast Cancer Patients with Axillary Lymph Node Metastasis: A Single Center Experience

Purpose

This study compared the survival outcomes of different treatment methods for the ipsilateral breast of occult breast cancer (OBC) patients with axillary lymph node metastasis.

Methods

A retrospective study was conducted in which forty OBC patients with axillary lymph node metastasis were identified out of 15,029 patients who had been diagnosed with a primary breast cancer at between 1992 and 2010. The patients were categorized into three treatment groups based on ipsilateral breast management: breast-conserving surgery (BCS) (n=17), mastectomy (n=12), and nonsurgical intervention with or without radiation therapy (No surgery with or without radiation therapy [No Op±RT]) (n=11). All patients underwent axillary lymph node dissection. Cases were evaluated based on treatment and potential prognostic factors with respect to overall survival (OS) and disease-free survival (DFS).

Results

During the follow-up period (median follow-up of 71.5 months), the overall OS and DFS were 76.9% and 74.9%, respectively. The 5-year treatment-specific OS was 72.0% for the BCS group, 74.0% for the mastectomy group, and 87.5% for the No Op±RT group (log-rank p=0.49). The 5-year DFS was 70.6% for the BCS group, 66.7% for the mastectomy group, and 90.9% for the No Op±RT group (log-rank p=0.36). Recurrence rates for the BCS and No Op±RT groups were 5.9% and 18.2%, respectively. Histologic grade and lymph node status were inversely correlated with DFS (log-rank p=0.04 and p<0.01, respectively).

Conclusion

There was no difference in survival outcomes between the three treatment methods for the ipsilateral breast (mastectomy, BCS, and No Op±RT) of OBC patients with axillary lymph node metastasis. A large-scale multicenter study is needed to validate the results from this small retrospective study.     

Pilot trial of paclitaxel-trastuzumab adjuvant therapy for early stage breast cancer: a trial of the ECOG-ACRIN cancer research group (E2198)

Background:

Blockade of human epidermal growth factor receptor type 2 (HER2) has dramatically improved outcome for patients with HER2-positive breast cancer. Trastuzumab, an anti-HER2 monoclonal antibody, has previously demonstrated improvement in overall survival (OS) in patients with metastatic and early stage HER2-positive breast cancer. However, trastuzumab can cause congestive heart failure (CHF) with an increased frequency for patients who have also received an anthracycline. The current trial was designed to evaluate the impact of the duration of trastuzumab on CHF.

Methods:

E2198 included 227 eligible women with histologically confirmed stage II or IIIA HER2-positive breast cancer. The patients were randomised to receive 12 weeks of paclitaxel and trastuzumab followed by four cycles of doxorubicin and cyclophosphamide (abbreviated Arm) or the aforementioned treatment with additional 1 year of trastuzumab (conventional Arm). The primary end point was to evaluate the safety of this variable duration of trastuzumab therapy, particularly cardiac toxicity defined as CHF or left ventricular ejection fraction decrease >10%. Secondary end points included disease-free survival (DFS) and OS.

Results:

Compared with 12-week treatment with trastuzumab, 1 year of trastuzumab-based therapy did not increase the frequency or severity of cardiac toxicity: three patients on the abbreviated Arm and four on the conventional Arm experienced CHF. The 5-year DFS was 76% and 73% for the abbreviated and conventional Arms, respectively, with a hazard ratio (HR) of 1.3 (95% CI: 0.8–2.1; P=0.3). There was also no statistically significance difference in OS (HR, 1.4; P=0.3).

Conclusions:

Compared with 12 weeks of treatment, 1 year of treatment with trastuzumab did not significantly increase the risk of cardiac toxicity. Although not powered for efficacy comparisons, the longer duration of trastuzumab therapy did not demonstrate a signal for marked superiority.     

Impact of anti-HER2 therapy on overall survival in HER2-overexpressing breast cancer patients with brain metastases

Background:

Trastuzumab-based therapy after diagnosis of brain metastases (BM) may improve survival due to prolonged systemic disease control. We investigated whether lapatinib may yield additional survival benefit.

Methods:

Eighty patients with BM from HER2-positive breast cancer were identified. Karnofsky Performance Score (KPS) of at least 70 was required. We included a control group of 37 patients treated before 2003, when continuation of trastuzumab after diagnosis of BM was not yet recommended. Remainders received either trastuzumab or lapatinib and trastuzumab (either concomitantly or sequentially) with or without chemotherapy.

Results:

Median overall survival (OS) in patients receiving trastuzumab after diagnosis of BM was 13 months; corresponding numbers were 9 months in patients treated with chemotherapy, and 3 months with radiotherapy alone. Median OS was not reached in the lapatinib group. Addition of lapatinib prolonged OS over trastuzumab alone (P=0.002). After correction for potential confounders, lapatinib therapy remained an independent positive predictor for survival (HR 0.279; P=0.012).

Interpretation:

This retrospective single-centre study suggests that the introduction of lapatinib improved survival in patients with BM from HER2-positive breast cancer. Patients with KPS ⩾70 may benefit when treated with lapatinib in addition to trastuzumab after completion of local therapy.     

Survival benefit of laparoscopic surgical staging-guided radiation therapy in locally advanced cervical cancer

Objective

This study was designed to evaluate the survival benefit of laparoscopic surgical staging (LSS)-guided tailored radiation therapy (RT) in locally advanced cervical cancer (LACC).

Methods

We retrospectively reviewed 89 LACC patients'' medical records who primarily received non-surgical treatment, of which pretreatment LSS was performed in 20 (LSS group) and primary chemoradiation therapy (CCRT) without LSS (CCRT group) was carried out in 69 from January 2000 to January 2006. We analyzed clinical characteristics, pretreatment imaging study results and survival outcomes including disease free survival (DFS) and overall survival (OS) to compare them between the two groups.

Results

There were as many as eight cases (40%) of LSS related complications. The mean time interval between LSS and RT or CCRT was 26.6 days (±18.8 days). Six out of twenty (30%) in LSS group and 10 out of 69 (14.5%) in CCRT group received extended field RT when paraaortic lymph nodes (LNs) were positive based on the pathologic findings after LSS and the results of imaging studies, respectively. Three-year DFS and OS were both better in 33 imaging-negative CCRT group patients than those in 4 imaging-negative/pathology-positive (false negative) patients after LSS (3-year DFS, 50% vs. 87%, p=0.022; 3-year OS, 50% vs. 84%, p=0.033). The 5-year DFS rates were 52% and 55% in LSS group and in CCRT group, respectively (p=0.28). The 5-year OS rates were 68% in LSS group and 62% in CCRT group without significant difference between the two groups (p=0.79).

Conclusion

We found that LSS-based RT tailoring did not show survival benefit in LACC despite inaccuracy of imaging-based RT tailoring. Further studies are required to find new method to overcome this inaccuracy and improve survival outcomes.     

Diastolic Dysfunction Occurs Early in HER2‐Positive Breast Cancer Patients Treated Concurrently With Radiation Therapy and Trastuzumab

Background.

Left ventricular ejection fraction (LVEF) is used routinely to monitor cardiac dysfunction associated with breast cancer treatment. In this study the prevalence of early left ventricular diastolic dysfunction (LVDD) and its relationship to the dose-volume of the heart irradiated were evaluated in HER2-positive breast cancer patients undergoing concurrent trastuzumab and adjuvant radiotherapy (RT).

Materials and Methods.

Data from 40 breast cancer patients treated with concurrent trastuzumab and left-sided adjuvant RT between September 2011 and October 2012 were collected prospectively. For comparison, 32 patients treated with concurrent trastuzumab and right-sided adjuvant RT and 71 patients treated with left-sided RT alone were collected retrospectively. Echocardiography was obtained before RT, immediately following RT, and 3 and 6 months after RT. Doses to the heart and left ventricle (LV) were quantified.

Results.

Prior to RT with concurrent trastuzumab, 11 of 29 (left) and 8 of 25 (right) patients with normal baseline left ventricular diastolic function (LVDF) developed LVDD. In patients receiving left-sided RT alone, 12 of 61 patients with normal baseline LVDF developed LVDD. D_mean, D₁₅–D₄₀, D₆₀–D₇₀, and V₃–V₁₀ of the LV were significantly higher in patients who developed LVDD after concurrent trastuzumab and left-sided RT. In contrast, only two patients developed grade 1 LVEF decrease after both concurrent treatment and left-sided RT alone.

Conclusion.

Changes in LVDF compared with LVEF are more sensitive for early detection of cardiotoxicity. The dose-volume of the heart contributes significantly to the risk of LVDD in patients with left-sided breast cancer treated concurrently with trastuzumab.

Implications for Practice:

Abnormalities in diastolic function are more sensitive than changes in the left ventricular ejection fraction for detecting acute cardiotoxicity and are related to the dose-volume of the heart irradiated in patients with left-sided breast cancer receiving radiotherapy concurrently with trastuzumab. This result highlights the importance of decreasing the dose-volume of heart irradiated as a protective strategy in the treatment setting of concurrent trastuzumab and radiotherapy. Diastolic dysfunction may serve as a more sensitive tool for the early detection of cardiac damage and should be incorporated as a routine parameter in the functional monitoring of cardiotoxicity.     

Comparison of anal cancer outcomes in public and private hospital patients treated at a single radiation oncology center

Objective

To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital.

Methods

We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks ≥10 days were compared using t-test and χ² test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed.

Results

The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks ≥10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis.

Conclusions

Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.     

Operable Breast Cancer of the Inner Hemisphere Is Associated with Poor Survival

Purpose

This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes.

Methods

Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location.

Results

The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed.

Conclusion

This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors.     

Feasibility of Sentinel Lymph Node Biopsy in Breast Cancer Patients with Initial Axillary Lymph Node Metastasis after Primary Systemic Therapy

Purpose

Primary systemic therapy (PST) downstages up to 40% of initial documented axillary lymph node (ALN) metastases in breast cancer. The current surgical treatment after PST consists of breast tumor resection and axillary lymph node dissection (ALND). This strategy, however, does not eliminate unnecessary ALND in patients with complete remission of axillary metastases. The aim of this study was to examine the accuracy of sentinel lymph node biopsy (SLNB) after PST among patients with documented ALN metastasis at presentation and to identify the rate of pathologic complete-remission (CR) with ALN after PST.

Methods

We analyzed 66 patients with ALN metastasis that was pathologically proven preoperatively who underwent SLNB and concomitant ALND after PST. Axillary ultrasound (AUS) was used to evaluate the clinical response of initially documented ALN metastasis after PST. Intraoperative lymphatic mapping was performed using blue dye with or without radioisotope.

Results

After PST, 34.8% of patients had clinical CR of ALN on AUS and 28.8% patients had pathologic CR of ALN. The overall success rate of SLNB after PST was 87.9%, and the sentinel lymph node identification rate in patients with clinical CR was 95.7%. In patients with successful lymphatic mapping, 70.7% of patients had residual axillary metastases. The overall accuracy and false-negative rate were 87.9% and 17.1% in all patients: 95.5% and 10.0% in patients with clinical CR of ALN, and 83.3% and 19.4% in patients with residual axillary disease after PST.

Conclusion

Our findings suggest that SLNB may be feasible in patients with initial documented ALN metastasis who have clinical CR for metastatic ALN after PST. Further investigation in a prospective setting should be performed to confirm our results.     

Survival analysis of endometrial cancer patients with cervical stromal involvement

Objective

Stage II endometrial cancer is relatively uncommon. There is no consensus for appropriate adjuvant therapy in endometrial cancer patients with cervical stromal involvement (International Federation of Gynecology and Obstetrics [FIGO] stage II). This study investigates how adjuvant treatments and tumor characteristics influence overall survival (OS) and disease-free survival (DFS) in stage II patients in order to establish better treatment guidelines.

Methods

This multi-institution, Institutional Review Board approved, study is a retrospective review of 40 endometrial cancer patients with cervical stromal involvement treated from 1993 to 2009. Kaplan-Meier estimates were used to evaluate OS and DFS.

Results

OS was 85% at three years and 67% at five years. There were no significant differences in age, histology, depth of invasion, comorbid conditions, surgical staging or recurrence between patients who received radiation therapy (RT) and those who did not. However, patients with FIGO grade 1 cancers were less likely to receive RT (p=0.007). Patients treated with RT had a similar 5 year OS (n=33, 69%) to those treated with surgery only (n=7, 60%, p=0.746). There were no OS differences when evaluating by grade, histology, or depth of invasion between patients who did and did not receive RT. Four patients recurred: three were locoregional failures only, and one failed locally and distant.

Conclusion

Patients receiving RT had higher grade tumors. Despite this, OS was comparable between the RT and the no RT cohorts. Local failure was the predominant pattern of failure. Endometrial cancer patients with cervical stromal involvement likely receive better locoregional control with the addition of adjuvant RT and we continue to advocate for RT in most cases.     

Treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy

Objective

To evaluate treatment outcomes and prognostic factors in uterine cervical cancer patients treated with postoperative extended field radiation therapy (POEFRT) with or without chemotherapy.

Methods

Between 1983 and 2006, 35 patients with a pathologically confirmed positive para-aortic node (PAN) or common iliac node (CIN) who underwent a radical hysterectomy with bilateral pelvic lymph node dissection and PAN dissection received POEFRT with (N=23) or without (N=12) chemotherapy. Prognostic factors such as age, stage, size, parametrium invasion, lymphovascular space invasion, nodal station, depth of stromal invasion and use of chemotherapy were analyzed.

Results

With a median follow-up of 44 months, the 5-year overall survival (OS), disease-free survival (DFS), distant failure-free survival (DFFS) and loco-regional failure-free survival rates were 51%, 51%, 59% and 93%, respectively. The use of chemotherapy significantly improved the 5-year OS rate (61% vs. 48%, p=0.004), the 5-year DFS rate (54% vs. 38%, p=0.004) and the 5-year DFFS rate (57% vs. 48%, p=0.009). PAN involvement resulted in a compromised 5-year DFS rate (42% vs. 73%, p=0.002) and 5-year DFFS rate (47% vs. 82%, p=0.004) as compared to CIN involvement. Grade 3 or higher hematological toxicity was observed more frequently in patients who received POEFRT combined with chemotherapy as compared to patients who received POEFRT alone (52% vs. 17%, p=0.04).

Conclusion

The use of POEFRT resulted in an excellent loco-regional control rate. The addition of chemotherapy may improve outcome in patients who have received POEFRT, but with higher manageable toxicity.     

Efficacy of Trastuzumab in Routine Clinical Practice and After Progression for Metastatic Breast Cancer Patients: The Observational Hermine Study

Background.

The Hermine study observed the use of trastuzumab for metastatic breast cancer (MBC) in routine practice, including patients who received trastuzumab treatment beyond progression (TBP).

Patients and Methods.

The study observed 623 patients for ≥2 years. Treatment was given according to oncologists'' normal clinical practices. Endpoints included duration of treatment, efficacy, and cardiac safety. The TBP subanalysis compared overall survival (OS) in 177 patients who received first-line trastuzumab and either continued trastuzumab for ≥30 days following progression or stopped at or before progression.

Results.

The median treatment duration was 13.3 months. In the first-, second-, and third-line or beyond treatment groups, the median time to progression (TTP) were 10.3 months, 9.0 months, and 6.3 months, and the median OS times were 30.3 months, 27.1 months, and 23.2 months, respectively. Heart failure was observed in 2.6% of patients, although no cardiac-associated deaths occurred. In the TBP subanalysis, the median OS duration from treatment initiation and time of disease progression were longer in patients who continued receiving trastuzumab TBP (>27.8 months and 21.3 months, respectively) than in those who stopped (16.8 months and 4.6 months, respectively). However, the groups were not completely comparable, because patients who continued trastuzumab TBP had better prognoses at treatment initiation. The median TTP was longer in patients who continued trastuzumab TBP (10.2 months) than in those who stopped (7.1 months).

Conclusion.

The Hermine findings confirm that the pivotal trials of first-line trastuzumab treatment in MBC patients are applicable in clinical practice. The subanalysis suggests that trastuzumab TBP offers a survival benefit to MBC patients treated with first-line trastuzumab.     

Pathological complete response and prognosis after neoadjuvant chemotherapy for HER2-positive breast cancers before and after trastuzumab era: results from a real-life cohort

Background:

Trastuzumab was introduced a decade ago and has improved outcomes for HER2-positive breast cancer. We investigated the factors predictive of pathological complete response (pCR), prognostic factors for disease-free survival (DFS), and interactions between pCR and DFS after neoadjuvant treatment.

Methods:

We identified 287 patients with primary HER2-positive breast cancers given neoadjuvant chemotherapy (NAC) between 2002 and 2011. Univariate and multivariate analyses of clinical and pathological factors associated with pCR and DFS were performed.

Results:

pCR rates differed between patients receiving neoadjuvant trastuzumab treatment or not (47.7% versus 19.3%, P<0.0001). DFS also differed significantly between patients receiving adjuvant trastuzumab or not (hazard ratio=4.84, 95% CI (2.52; 9.31), P<0.001). We analysed 199 patients given neoadjuvant and adjuvant trastuzumab. Multivariate analysis identified older age and hormone receptor-negative tumours as independent predictors of pCR. T stage (hazard ratio=2.55, 95% CI (1.01; 6.48), P=0.05) and strict pCR (hazard ratio=9.15, 95% CI (1.22; 68.83), P=0.03) were independent predictors of DFS. The latter association was significant in the HR-negative subgroup (P=0.02) but not in the HR-positive subgroup (P=0.12).

Conclusions:

Major pCR and DFS gains in HER2-positive BC were observed since ‘trastuzumab'' era. Further improvements rely on the enrollment of accurately selected patients into clinical trials.     

Clinical evaluation of stereotactic radiation therapy for recurrent or second primary mediastinal lymph node metastases originating from non-small cell lung cancer

Aims

To evaluate the safety and efficacy of stereotactic radiotherapy (SRT, both stereotactic body RT [SBRT] and fractionated stereotactic RT [FSRT]) in the treatment of patients with recurrent or second primary mediastinal lymph node metastases (R/SP-MLNMs) originating from non-small cell lung cancer (NSCLC).

Methods

Between 10/2006 and 7/2013, patients with R/SP-MLNMsoriginating from NSCLC were enrolled and treated with SRT at our hospital; their data was stored in prospectively-collected database. The enrolled patients were divided into Group A (without prior RT) and Group B (with prior RT). The primary end-point was overall survival (OS). The secondary end-points were the MLNM local control (LC), the time to symptom alleviation, and toxicity using the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Results

Thirty-three patients were treated (16 in Group A with 19 R/SP-MLNMs and 17 in Group B with 17 R/SP-MLNMs). For the entire cohort, the median OS was 25.5 months with a median follow-up of 20.9 months (range, 3.2-82). The 1-year and 3-year actuarial LC rates were 100% and 86%, respectively. Symptom alleviation was observed in 52% of patients, after a median of 6 days (range, 3-18). CTCAE v4.0 ≥ Grade 3 toxicities occurred in 5 patients (15%; all in Group B); among them, Grade 5 in 2 patients.

Conclusions

We recommend exercising extreme caution in using SRT for R/SP-MLNMs in patients who received prior RT (particularly to LN station 7). For patients without previous RT, SRT appears to be safe and efficacious treatment modality; prospective studies are warranted.     

Comparison of the Characteristics of Medullary Breast Carcinoma and Invasive Ductal Carcinoma

Purpose

Medullary breast carcinomas (MBC) have been known to represent a rare breast cancer subtype associated with a more favorable prognosis than invasive ductal carcinomas (IDC). The purpose of this study was to compare the clinicopathologic characteristics and outcomes of MBC with those of IDC.

Methods

We retrospectively reviewed medical records of patients with invasive breast cancer who were managed surgically from August 1995 to June 2010.

Results

Fifty-two patients were identified with MBC and 5,716 patients were identified with IDC. The clinicopathologic features, disease-free survival (DFS), and overall survival (OS) of patients with MBC were compared with those of patients with IDC. The MBC group presented at a younger age (p=0.005) and had a significant association with a higher histological grade (p=0.003) and nuclear grade (p<0.001) as well as negative estrogen receptor (p<0.001) and progesterone receptor (p<0.001) status. Lymphatic invasion was absent (p<0.001) and lymph node metastasis was rare (p<0.001). The DFS and OS did not differ significantly between the two groups (5-year DFS: 88.0% vs. 89.2%, p=0.920; 5-year OS: 93.4% vs. 94.4%, p=0.503). In multivariate analysis, the factors associated with DFS and OS were nuclear grade, histological grade, tumor size, lymph node metastasis, estrogen receptor status, progesterone receptor status, and human epidermal growth factor receptor 2 status, chemotherapy, and hormone therapy. However, DFS and OS were not significantly different between IDC and MBC according to histological type itself (DFS: hazard ratio 0.85, 95% confidence interval 0.12-6.05, p=0.866; OS: hazard ratio 1.49, 95% confidence interval 0.21-10.77, p=0.692).

Conclusion

Although MBC has specific clinicopathologic features, its prognosis does not differ from IDC and is determined by prognostic factors such as tumor size and lymph node metastasis. Therefore, patients with MBC also require the same intensive treatment provided for IDC.     

Comparative effectiveness study of breast-conserving surgery and mastectomy in the general population: A NCDB analysis

Purpose

Recent studies have revealed that breast-conserving surgery (BCS) with radiotherapy (RT) led to better survival than mastectomy in some populations. We compared the efficacy of BCS+RT and mastectomy using the National Cancer Database (NCDB, USA).

Methods

Non-metastatic breast cancers in the NCDB from 2004–2011 were identified. The Kaplan-Meier method, Coxregression and propensity score analysis were used to compare the overall survival (OS) among patients with BCS+RT, mastectomy alone and mastectomy+RT.

Results

A total of 160,880 patients with a median follow-up of 43.4 months were included. The respective 8-year OS values were 86.5%, 72.3% and 70.4% in the BCS+RT, mastectomy alone and mastectomy+RT group, respectively (P < 0.001). After exclusion of patients with comorbidities, mastectomy (alone or with RT) remained associated with a lower OS in N0 and N1 patients. However, the OS of mastectomy+RT was equivalent to BCS+RT in N2–3 patients. Among patients aged 50 or younger, the OS benefit of BCS+RT over mastectomy alone was statistically significant (HR1.42, 95% CI 1.16–1.74), but not clinically significant (<5%) in N0 patients, whereas in N2–3 patients, the OS of BCS+RT was equivalent to mastectomy+RT (85.2% vs. 84.8%). The results of the propensity analysis were similar.

Conclusions

BCS+RT resulted in improved OS compared with mastectomy ± RT in N0 and N1 patients. In N2–3 patients, BCS+RT has an OS similar to mastectomy+RT when patients with comorbidities were excluded. Among patients aged 50 or younger, the OS of BCS+RT is equivalent to mastectomy ± RT.     

Continued Use of Trastuzumab Beyond Disease Progression in the National Comprehensive Cancer Network: Should We Practice Ahead of the Evidence?

Background.

The role of continued trastuzumab after progression in women with human epidermal growth factor receptor (HER)-2⁺ metastatic breast cancer is controversial. Controlled clinical trials that establish a benefit from continued trastuzumab have been difficult to complete.

Methods.

In the National Comprehensive Cancer Center Network (NCCN) Breast Cancer Outcomes Database, we identified women treated with trastuzumab for metastatic or relapsed HER-2⁺ breast cancer at eight NCCN centers who subsequently progressed. Patients were eligible for this analysis if they initiated treatment at an NCCN institution between July 1997 and December 2004, received trastuzumab-containing treatment, and progressed while on therapy. We calculated the proportion of patients who received trastuzumab after progression, and in a multivariate analysis assessed the association of patient and provider characteristics with continued trastuzumab therapy.

Results.

Our final cohort consisted of 218 women who experienced disease progression while on trastuzumab-containing therapy. Of these, 168 (77%) continued trastuzumab. Of these, 36 patients (17%) received therapy as part of a clinical trial. The only factors significantly associated with continuation of trastuzumab beyond progression were the presence of bone metastases and more recent year of development of progressive disease.

Conclusions.

Prior to the availability of any high-quality evidence supporting this practice, over three quarters of patients treated with trastuzumab for HER-2⁺ metastatic breast cancer at eight NCCN centers continued therapy beyond progression. Further work is needed to understand how physicians adopt new treatments when there is ambiguity surrounding their benefit.     

Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy

Purpose:

To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST).

Patients and methods:

Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan–Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed.

Findings:

Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively).

Conclusions:

In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.     

Impact of margin status and lymphadenectomy on clinical outcomes in resected pancreatic adenocarcinoma: implications for adjuvant radiotherapy

Background

Adjuvant chemoradiotherapy (CRT) in the treatment of pancreatic ductal adenocarcinoma (PDA) is controversial. Minimal data exists regarding the clinical significance of margin clearance distance and lymph node (LN) parameters, such as extent of dissection and LN ratio. We assessed the impact of these variables on clinical outcomes to more clearly define the subset of patients who may benefit from adjuvant radiotherapy (RT).

Methods

We identified 106 patients with resected stage 1-3 PDA from 2007-2013. Resection margins were categorized as positive (tumor at ink), ≤1, or >1 mm. LN evaluation included total number examined (NE), number of positive nodes (NP), ratio of NP to NE (NR), extent of dissection, and positive periportal LNs. The impact of these variables was assessed on disease-free survival (DFS) and overall survival (OS) using multivariate cox proportional hazards modeling.

Results

In patients receiving adjuvant chemotherapy (CT) alone, greater margin clearance led to improved DFS (P=0.0412, HR =0.51). Range of NE was 4-37, with a mean of 19. NE was not associated with DFS or OS, yet absolute NP of 5 or more was associated with a significantly worse DFS (P=0.005). Whereas periportal lymphadenectomy did not result in improved DFS or OS, patients with positive periportal LN had worse clinical outcomes (DFS, P=0.0052; OS, P=0.023). The use of adjuvant CRT was associated with improved OS (P=0.049; HR=0.29).

Conclusions

In patients receiving adjuvant CT alone, there was a clinically significant benefit to clearing the surgical margin beyond tumor at ink. Having ≥5 NP and positive periportal LN led to significantly worse clinical outcomes. The addition of adjuvant RT to CT in resected PDA improved OS. A comprehensive evaluation of resection margin distance and LN parameters may identify more patients at risk for locoregional failure who may benefit from adjuvant CRT.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal and hepatic metastases: a case-control study

Background

Concomitant treatment of colorectal peritoneal metastases (PM) and hepatic metastases (HM) remains controversial. This study compares the cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal metastases (PM) with the CRS/IPC/hepatic resection treatment of colorectal PM and HM.

Methods

All patients from a prospective PM registry at the Uppsala institution treated concomitantly for PM/HM with CRS/IPC/hepatic resections were included in a PM/HM-group, n=11. They were matched 1^:2 with patients from the registry being treated only for PM with CRS/IPC, n=22. Overall survival (OS), disease-free survival (DFS), morbidity, mortality, and recurrences were compared.

Results

The PM/HM-group had median OS of 15 months (95% CI: 6-46 months) and the PM-group had a median OS of 34 months (95% CI: 19-37 months), P=0.2. The DFS was 10 months (95% CI: 3-14 months)
and 24 months (95% CI: 10-32 months) respectively, P=0.1. Morbidity was 27% in both groups and one postoperative death in the PM/HM-group. Currently, 1/10 (10%) patients with an R1 resection are
disease-free in the PM/HM group while 9/20 (45%) are disease-free in the PM group (P=0.05).

Conclusions

Concomitant treatment of PM and HM with CRS/IPC/hepatic resections is feasible with no significant increase in morbidity compared to CRS/IPC. The risk of recurrences is higher in the PM/HM group with a tendency towards worse DFS.Key Words: Colorectal cancer, peritoneal carcinomatosis, peritoneal metastases, hepatic metastases, cytoreductive surgery, intraperitoneal chemotherapy     

Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis

Purpose

Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer.

Methods

We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression.

Results

There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73).

Conclusion

Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes.