Pre-surgical chemotherapy for breast cancer may be associated with improved outcomes

Background

Historical studies suggest no difference in disease outcome between neoadjuvant and adjuvant approaches in breast cancer. We hypothesize neoadjuvant chemotherapy (NCT) may offer several benefits, possibly improving quality of life outcomes.

Breast cancer in patients with schizophrenia

Background

Schizophrenia has a powerful impact on the outcomes of treatment for physical disorders. This study sought to estimate how the presence of schizophrenia disrupts the course of diagnosis and initial treatment of breast cancer.

Methods

We searched the Patient Treatment File, a comprehensive computer-based system for inpatient data in the Department of Veterans Affairs (DVA) medical system, to identify patients with codes for schizophrenia or schizoaffective disorder who later developed breast cancer. These data were augmented with chart-based clinical data.

Results

There were 56 evaluable patients from 34 DVA facilities; 37 (66%) were female. Delay in diagnosis was common. The mean size of the primary tumor was 4 cm in those for whom these data were recorded. Delay in diagnosis was common and many never received the indicated surgery. Distant metastases were present on diagnosis in 12 (21%) and developed after diagnosis in 14 (25%) others, including 7 who inappropriately delayed or refused indicated surgery and 4 who inappropriately delayed or refused indicated neoadjuvant chemotherapy. Twelve verbally abused or physically attacked caregivers.

Conclusions

Patients with schizophrenia who later develop breast cancer often deny they have cancer. They often have high-stage disease at diagnosis and often delay or refuse therapy. Breast-conserving multimodality therapy is often not feasible.     

Administration of ketamine during induction and maintenance of anaesthesia in postoperative pain prevention

Introduction

Carcinologic breast surgery is responsible of intermediary postoperative pain and needs 30% additional morphine. Now, morphine administration generates adverse effects. Publications about morphine saving effect of ketalar as antagonist of R-NMDA, administrated in perioperative increase are discussed.

Objective

To evaluate the morphine saving effect of ketalar in carcinologic breast surgery.

Patients and method

This phase III randomized and double-blind study includes 208 patients during 14 months. Surgery consisted in mastectomy with or without axillary lymph node dissection or lumpectomy with axillary lymph node dissection. Group K received ketalar at induction until the end of surgery. Group P (placebo) received physiologic serum in the same condition. During the postoperative first 48 h, morphine's consumption and EN are measured.

Results

No significant difference between two groups was observed. The EN evaluation and morphine consumption remained the same in the two groups. Our results did not find any benefit with use of ketamine between axillary lymph node dissection and no axillary lymph node dissection group.

Conclusion

Ketalar adjunction in our analgesic protocol did not induce significant morphine saving in carcinologic breast surgery.     

Taxanes in combination with cisplatin and fluorouracil for advanced penile cancer: preliminary results

Background

Chemotherapy is emerging in the management of advanced penile cancer.

Objective

To evaluate the therapeutic activity of taxanes (T) in combination with cisplatin-fluorouracil (PF) for salvage of primarily unresectable or relapsed nodal metastases from squamous cell carcinoma (SCC) of the penis.

Design, setting, and participants

Six consecutive patients were treated at Istituto Nazionale Tumori (INT), Milano, with neoadjuvant paclitaxel, cisplatin, and 5-fluorouracil (TPF) for unresectable (two cases) or recurrent nodal metastases (four cases) from SCC of the penis from 2004 to 2006. Informed consent was given by all patients.

Intervention

Four courses of neoadjuvant TPF were to be given before salvage surgery.

Measurements

Patients underwent computed tomography (CT) scans before starting chemotherapy, after two courses, and at the end of chemotherapy. Lymph node dissection was to be performed in responsive patients.

Results and limitations

Two patients received more than four courses: Both had pathologically documented complete remission, and they are alive and disease free >2 yr after chemotherapy. The other four patients received only two courses. The first patient had subjective intolerance to TPF: He underwent early postchemotherapy radical lymph node dissection, which documented >90% tumour necrosis: He is alive and disease free 46 mo after starting chemotherapy. Of the other three patients, one was not responsive, changed therapy, and died within 4 mo. The other two had a clinical complete remission after the first two courses. Both refused to complete chemotherapy, and they relapsed after 10 and 4 mo. Limitations are the small number of patients and protocol violation in three cases.

Conclusions

TPF chemotherapy for unresectable or recurrent nodal metastases from SCC of the penis is promising, and the standard four courses of therapy are to be completed in responding patients. A larger series is necessary to confirm preliminary results.     

The clinical impact and outcomes of immunohistochemistry-only metastasis in breast cancer

Background

Modern surgical and pathological techniques can detect small-volume axillary metastases in breast cancer with unknown clinical significance.

Methods

A retrospective database review from 1996 through 2004 identified all patients with immunohistochemical (IHC)-only sentinel node (IHC-SN) metastases and compared them with negative controls (Neg-SN).

Results

When comparing the 232 IHC-SN patients with the 252 Neg-SN controls, the IHC-SN patients had larger tumors, more lobular histology, a higher grade, and more HER2/neu positivity. They also received more systemic therapy. With a median follow-up of 5 years, there were no differences in recurrence-free survival or overall survival. In 123 IHC-SN patients treated with axillary dissection (axillary lymph node dissection), 16% had positive non-SLNs. Patients with positive non-SLNs tended to have worse outcomes.

Conclusions

IHC-only sentinel lymph node (SLN) metastases were associated with worse prognostic features and higher rates of systemic therapy. However, no outcomes differences were noted.     

Recurrence rates in breast cancer patients with false-negative intraoperative evaluation of sentinel lymph nodes

Background

Intraoperative identification of sentinel lymph node (SLN) metastases in breast cancer patients results in synchronous axillary lymph node dissection. We examined the effect of false-negative SLN biopsy on breast cancer treatments and recurrence rate.

Methods

Patient and tumor characteristics, intraoperative and final SLN biopsy results, and treatments of patients with and without recurrence were compared.

Results

Recurrence rates for patients with true-positive SLN biopsy (9%) were significantly higher than rates for false-negative SLN biopsy patients (2%). Recurrence rates were significantly higher for patients with primary tumors greater than 2 cm, positive lymph nodes greater than 2 mm, and tumors with negative hormone receptors, and varied with treatment extent.

Conclusions

Patients with greater amounts of disease in the breast and axilla required more treatment and had a higher recurrence rate. False-negative SLN evaluation occurred more commonly in patients with less lymph node metastasis and was not associated with an increased recurrence rate.     

Regional recurrence in the era of sentinel lymph node biopsy

Background

The incidence of all-location regional recurrence after sentinel lymph node biopsy is not well documented. This study attempts to identify risk factors.

Methods

A prospectively maintained database was queried to identify patients with a regional recurrence of breast cancer after a first operation for invasive unilateral breast cancer. Patients with regional recurrence were compared with those alive and disease free at 5 years.

Results

Twenty-one of 1,060 patients (2%) experienced a regional recurrence. Most patients (95%) underwent sentinel lymph node biopsy as their axillary staging. Those with regional recurrences had larger tumors (P < .001), higher stage disease (P < .001), more estrogen receptor– and triple-negative breast cancers (P < .001), and more positive lymph nodes (P = .007). Mastectomy (P = .001) and receipt of neoadjuvant and/or chemotherapy (P < .001) were more common among those with regional recurrences.

Conclusions

Regional recurrence of breast cancer occurs infrequently. Risk factors include high-risk cancers, higher stage at presentation, nodal involvement, and need for therapies reflecting higher risk biology.     

Neoadjuvant therapy and breast cancer surgery: a closer look at postoperative complications

Background

Neoadjuvant therapy is important in the treatment of advanced breast cancer.

Methods

Postoperative complications in neoadjuvant patients were analyzed.

Results

One hundred forty patients underwent 148 breast cancer surgeries after neoadjuvant therapy: 28% breast-conserving therapy procedures, 36% mastectomies, 28% mastectomies with immediate reconstruction, and 8% mastectomies with delayed reconstruction. Forty-seven patients (34%) suffered 59 complications: 18% of those undergoing breast-conserving therapy, 30% of those undergoing mastectomy, 44% of those undergoing mastectomy with immediate reconstruction, and 67% of those undergoing mastectomy with delayed reconstruction. Major complications occurred in 18% of patients. Skin loss occurred in 6% of patients. One patient had partial nipple necrosis. Three patients suffered implant loss. One patient had deep inferior epigastric artery perforator flap loss. Eleven hematomas and 5 infectious complications required reoperation.

Conclusions

Surgery after neoadjuvant therapy is safe, but careful counseling is warranted given that 18% of patients experienced major complications. Complications rates are higher with reconstruction, but feared complications of skin, nipple, implant, or flap loss were infrequent.     

Is sentinel lymph node biopsy a viable alternative to complete axillary dissection following neoadjuvant chemotherapy in women with node-positive breast cancer at diagnosis? An updated meta-analysis involving 3,398 patients

BACKGROUND

The use of sentinel lymph node biopsy (SLNB) following neoadjuvant chemotherapy (NAC) in patients presenting with clinically positive lymph nodes remains controversial.

Methods

A computer-aided search of the literature regarding SLNB in clinically node-positive breast cancer treated with NAC was carried out to identify the false negative rate (FNR), sentinel lymph node identification rate (IR), and axillary pathological complete response (pCR).

Results

Nineteen articles were used in the analysis yielding 3,398 patients. The pooled estimate of the FNR was 13% and that of the IR was 91%. The adjusted pCR rate was 47%. A trend toward significance was observed with only clinical stage N1 (cN1) disease whereby clinical stage N1 was associated with an increased pCR rate when compared to N2 or N3 disease (P = .06).

Conclusions

SLNB after NAC in biopsy-proven node-positive patients results in reasonably acceptable FNR and IR, making it a valid alternative management strategy to axillary dissection. More refined patient selection and optimal techniques can improve the FNR and IR in this patient population.     

Sentinel Lymph Node Biopsy is Precise After Primary Systemic Therapy in Stage II–III Breast Cancer Patients

Background

Sentinel lymph node biopsy (SLNB) without axillary lymph node dissection (ALND) in SLN negative patients is a standard of care for most breast cancer patients. SLNB for axillary staging after primary systemic therapy (PST) is still under discussion because of possibly reduced accuracy, while data are lacking. The purpose of this study was to evaluate the accuracy of SLNB after PST.

Materials and Methods

A total of 185 breast cancer patients were treated with PST; 160 patients received preoperative chemotherapy, and 25 patients received preoperative endocrine therapy. Thus, 143 of 160 patients with preoperative chemotherapy and 22 of 25 patients with preoperative endocrine therapy were eligible for evaluation. The combination of blue dye and radioactive tracer was used for identification of SLNs. All patients received SLNB and axillary lymph node dissection (ALND). Pathologic assessment of SLNs was performed and compared to non-SLN status.

Results

Pathologic complete response rates and breast conserving therapy rates were 15.4 and 78.3% in the preoperative chemotherapy group and 0 and 77.3% in the preoperative endocrine therapy group, respectively. Identification rate, sensitivity, overall accuracy, and false-negative rate were 81.1% (116 of 143), 91.7% (55 of 60), 95.7% (111 of 116), and 8.3% (5 of 60) in the preoperative chemotherapy group and 77.3% (17 of 22), 90.0% (9 of 10), 94.1% (16 of 17), and 10.0% (1 of 10) in the preoperative endocrine therapy group, respectively.

Discussion

SLNB after primary systemic therapy is accurate, and the results are comparable to those of primary SLNB. SLNB after PST could spare ALND in up to 40% of patients with primary positive axillary lymph nodes and should be considered as a standard for axillary staging in those patients.

     

Selective lateral compartment neck dissection for thyroid cancer

Background

Compartment-oriented lymph node dissection in patients with thyroid cancer and macroscopic lymph node metastases reduces recurrence and improves survival. However, the extent of lymph node dissection remains controversial. The purpose of this study was to examine the results of selective lateral compartment neck dissection (LCND) for thyroid cancer.

Methods

We completed a retrospective review of patients with thyroid cancer who underwent selective LCND from 1992–2012 to determine the extent of lymph node resection, morbidity, recurrence, subsequent operations, mortality, and duration of follow-up.

Results

A total of 45 LCNDs (five bilateral) were performed in 40 patients, 35 with differentiated thyroid cancer (DTC) and five with medullary carcinoma. Nineteen LCNDs (42%) were completed at the time of thyroidectomy. Levels IIA, III, IV, and VB were included in 43 LCNDs (96%) and levels IIA, III, and IV in two LCNDs (4%). Morbidity included neck or ear numbness in 19 patients (48%), neuropathic symptoms in 14 (35%), Horner syndrome in two (5%), marginal mandibular nerve paresis in two (5%), and wound infection in one (3%). Recurrence rate was 25% (10 patients) and one or more reoperations were performed in seven patients (18%) with a mean follow-up of 58 ± 60 mo (range, 1–244 mo). There were 3 ipsilateral recurrences (8%) after 40 LCNDs for DTC. Four patients died from systemic disease: three with medullary carcinoma and one with PTC.

Conclusions

Selective LCND is an effective therapeutic strategy for macroscopic lymph node metastases, with an 8% recurrence rate in the ipsilateral neck in patients with DTC. Neuropathic symptoms, however, remain an important source of morbidity.     

Axillary Lymph Node Status in Multicentric Breast Tumors and Breast Tumors with Nipple Involvement

Background

Axillary lymph node dissection plays an important role in breast cancer management in terms of staging, prediction of prognosis, determination of adjuvant therapy, and local control of the primary tumor. The objective of this study was to evaluate the axillary lymph node involvement in multicentric breast tumors and breast tumors with nipple involvement in comparison with unifocal tumors.

Patients and Methods

We reviewed the records of 267 patients with stage I or IIA disease. The rates of axillary lymph node metastasis (ALNM) in patients with unifocal tumors, multicentric tumors, or nipple involvement were compared.

Results

209 (78%) patients had unifocal tumors, 24 (8%) had multicentric tumors, and 34 (12%) had nipple involvement. The incidence of ALNM was 9.76% in patients with unifocal tumors, 24.84% in patients with multicentric tumors, and 36.71% in patients with nipple involvement. Hence, the incidence of ALNM was significantly higher in patients with nipple involvement or multicentric tumors than in patients with unifocal tumors.

Conclusion

Our data suggest that compared to unifocal tumors, breast tumors with nipple involvement or multiple foci show a significantly higher incidence of ALNM which is a predictor of a poor prognosis.     

Value of the pretreatment albumin to globulin ratio in predicting long-term mortality in breast cancer patients

Background

Prior studies have demonstrated the prognostic value of pretreatment serum albumin in different types of cancer. The aim of this study was to assess the predictive value of the albumin to globulin ratio (AGR) on survival in breast cancer patients.

Methods

This retrospective study used an unselected cohort of 354 breast cancer patients who had documented total protein and albumin levels prior to chemotherapy. Survival status was obtained from our cancer registry. Survival analysis, stratified by AGR tertiles, was used to evaluate the prognostic value of AGR.

Results

Patients in the highest AGR tertiles (AGR > 1.45) had a lower 5-year mortality rate compared with those in the middle (AGR 1.21 to 1.45) and the lowest (AGR < 1.21) tertiles (6% vs 18% and 32%, P < .001). After adjusting for confounding variables, AGR remained a significant predictor of mortality (P < .002). Moreover, after excluding the patients with albumin levels less than 3.6, the AGR remained a significant predictor of survival (P .0018).

Conclusions

Pretreatment AGR is an independent, significant predictor of long-term mortality in breast cancer patients, even in patients with normal albumin levels.     

Favorable Outcome of Secondary Axillary Dissection in Breast Cancer Patients with Axillary Nodal Relapse

Purpose

Little evidence can be found about the long-term outcome of breast cancer patients after axillary lymph node recurrence (ALNR) and its survival benefit after different kinds of management. The present study intends to evaluate the risk factors associated with axillary recurrence after definite surgery for primary breast cancer. The prognosis after ALNR and particularly outcome of different management methods also were studied.

Methods

We retrospectively reviewed data from 4,473 patients who were diagnosed with primary breast cancer and received surgical intervention in a single institute from January 1990 to December 2002. Medical files were reviewed and data on survival were updated annually. Risk factors and prognosis of patients with axillary recurrence were analyzed. Breast–cancer-specific survival of patients with ALNR and outcomes after different management methods also were studied.

Results

After a median follow-up of 70.2 months, axillary recurrence developed in 0.8% of patients. Factors associated with ALNR included: age younger than 40 years, medial tumor location, no initial standard level I &; II axillary dissection, and not receiving hormonal therapy. The 5-year breast–cancer-specific survival after ALNR was 57.9%. For patients who received further axillary dissection, the 5-year survival rate was 82.5% compared with 44.9% for patients who did not receive further dissection.

Conclusions

ALNR is a rare event in treating breast cancer. Young age at diagnosis and medially located tumor are associated with higher risk, but standardized initial axillary dissection to level II and adjuvant hormonal therapy is protective against ALNR. In patients with ALNR, the outcome is not dismal and survival may be improved if further axillary dissection is given.     

Biology of the estrogen receptor,GPR30, in triple negative breast cancer

Background

Triple-negative (TN) breast cancer lacks a known signaling pathway amenable to targeted therapy. The authors hypothesized that the G protein–coupled receptor GPR30 may be present in TN breast cancer and serve a role for tumor growth.

Methods

A retrospective pathology study and chart review were conducted. All patients aged ≤49 years from 2000 to 2008 were included (n = 24). Concurrent patients aged ≥50 years were randomly selected. Paraffin sections were stained for GPR30 and reviewed by a pathologist blinded to estrogen receptor and progesterone receptor status. Disease-free survival was analyzed versus age and receptor status. Means were compared using 2-sample t tests and proportions using chi-square analysis.

Results

Twenty-seven patients tested GPR30 positive and 21 GPR30 negative. Seventeen of 18 TN cancers tested positive for GPR30 (P < .0001). Recurrence at a mean follow-up of 36 months was 22.2% in the GPR30-positive group and 9.5% in the GPR30-negative group.

Conclusions

GPR30 is prevalent in TN breast cancer and associated with young age and possibly recurrence.     

Surgical treatment in Paget's disease of the breast

Background

The aim of this study was to evaluate the outcomes of surgical treatment of Paget's disease of the breast, with special emphasis on magnetic resonance imaging (MRI) and sentinel node biopsy (SNB).

Methods

The study included 58 consecutive patients with Paget's disease treated from 1995 to 2006.

Results

Twenty-five patients had ductal carcinoma in situ, and 31 had invasive carcinoma. MRI was performed in 14 patients, with positive findings in 7 patients, 5 of whom had negative findings on conventional imaging. The overall mastectomy rate was 76%. Eighteen patients underwent SNB, and 26 patients underwent full or partial axillary clearance. Fourteen patients had no axillary surgery. One patient had local recurrence after breast conservation, and another had axillary recurrence after negative results on SNB. Six patients had distant metastases. Four patients died of breast cancer.

Conclusions

Paget's disease is frequently associated with peripheral or multicentric cancer. MRI may be helpful when considering breast conservation or omitting axillary nodal staging.     

Aberrant expression of decoy receptor 3 in human breast cancer: relevance to lymphangiogenesis

Background

Decoy receptor 3 (DcR3), a decoy receptor against Fas ligand belonging to the tumor necrosis factor receptor superfamily, is overexpressed in some forms of cancer. It was recently reported that DcR3 could protect endothelial cells from apoptosis, implying a potential role in the development of vessels, whereas its role in the lymphangiogenesis remains unclear. In the present study, we studied the DcR3 expression and its relationship with the lymphatic microvessel density (LMVD) to investigate if it played a role in the lymph metastasis of human breast cancer.

Materials and methods

Real-time polymerase chain reaction and immunohistochemistry were performed to measure the messenger RNA and protein expression of DcR3 in the breast cancer tissues, noncancerous counterparts, and axillary lymph node from 63 patients. LMVD in these specimens was assessed by counting the D2-40 labeled–microvessels. Furthermore, the correlations between DcR3 expression and LMVD and other clinicopathologic parameters were analyzed.

Results

DcR3 was overexpressed in the breast cancer tissue of 58 patients (92.1%) and was also expressed in vascular endothelial cells and tumor cells in the lymph nodes. LMVD in cancer tissue and lymph nodes were both positively correlated to the aberrant expression of DcR3.

Conclusions

The relevance between DcR3 overexpression and LMVD revealed the existence of possible links between DcR3 and lymphangiogenesis. Based on these findings, it is important to further explore the regulation of lymphangiogenesis operated by the reverse tumor necrosis factor signaling of DcR3.