Node-negative Tumors Research Articles

Chemotherapy Use and Surgical Treatment by Receptor Subtype in Node-Negative T1a and T1b Female Breast Cancers, Iowa SEER Registry, 2010- to 2012

BackgroundPatients with small node-negative breast tumors who are younger or who have human epidermal growth factor receptor 2–positive (HER2+) or triple-negative breast cancer (TNBC) subtypes are at increased risk of recurrence. Concurrently, systemic treatment recommendations have evolved. Less is known about how frequently cytotoxic chemotherapy is given to these patients. Mastectomy rates have also increased. This study reports the recent incidence of T1a,bN0M0 breast cancer and the characteristics associated with chemotherapy delivery and the surgery selected. Patients and MethodsThis retrospective cohort is composed of invasive female breast cancers diagnosed with American Joint Committee on Cancer (AJCC) stage T1a,bN0M0 during 2010 to 2012 from the Iowa Surveillance, Epidemiology, and End Results (SEER) Cancer Registry. Chemotherapy use and surgery were identified by the registry. Univariate and multivariate analyses were performed to determine patient differences across subtype and factors associated with treatment. ResultsThe study included 1687 patients. This represented 27.6% of all AJCC stages I(a-c) to III breast cancer in 2010 to 2012, up from 18% in 1990 (P < .0001). Of 1456 patients with known subtype, 8.8% and 6.4% had HER2+ and TNBC disease, respectively. Chemotherapy was given to 7.5% of women with T1aN0M0 and 12.7% of T1bN0M0 tumors. The likelihood of systemic treatment was associated with breast cancer subtype, tumor differentiation, and age in a multivariate model. The mastectomy rate was 31.8%. ConclusionSmall node-negative breast cancers continue to grow significantly as a percentage of invasive breast cancer diagnoses. In 2010 to 2012 in Iowa, systemic chemotherapy correlated with risk factors associated with recurrence: age, subtype, and tumor differentiation. Relatively high rates of mastectomy were seen.

Recent prediagnostic aspirin use, lymph node involvement, and 5-year mortality in women with stage I-III breast cancer: a nationwide population-based cohort study.

Lymph node-positive breast tumors are more likely to express COX2 than node-negative tumors. In preclinical studies, COX2 inhibition prevents breast tumor spread to lymph nodes. Therefore, we examined the association between recent (1 year) prediagnostic use of aspirin (COX1/COX2 inhibitor), lymph node involvement at breast cancer diagnosis, and breast cancer-specific mortality. Women with stage I-III breast cancer diagnosed from 2001 to 2006 (N = 2,796) were identified from Ireland's National Cancer Registry. These data were linked to prescription refill and mammographic screening databases. Relative risks (RR) were estimated for associations between prediagnostic aspirin use and lymph node-positive status at diagnosis. HRs were estimated for associations between pre- and postdiagnostic aspirin use and 5-year mortality, stratified by lymph node status. Women with prediagnostic aspirin use were statistically significantly less likely to present with a lymph node-positive tumor than nonusers [RR = 0.89; 95% confidence interval (CI), 0.81-0.97], particularly those with larger (Pinteraction = 0.036), progesterone receptor (PR)-negative (Pinteraction < 0.001) or estrogen receptor (ER)-negative (Pinteraction = 0.056) tumors. The magnitude of this association increased with dose (Ptrend < 0.01) and dosing intensity (Ptrend < 0.001) and was similar in women with or without screen-detected tumors (Pinteraction = 0.70). Prediagnostic aspirin use was associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors (HR, 0.55; 95% CI, 0.33-0.92) but not node-positive tumors (HR, 0.91; 95% CI, 0.37-1.22). Tests for effect-modification were, however, not statistically significant (Pinteraction = 0.087). Postdiagnostic aspirin use was not associated with breast cancer-specific mortality (HR, 0.99; 95% CI, 0.68-1.45). Our findings indicate that recent prediagnostic aspirin use is protective against lymph node-positive breast cancer. This is a plausible explanation for reductions in breast cancer mortality reported in observational studies of aspirin use.

Optimal Management of Esophageal Adenocarcinoma: Should We Be CROSS?

by Surgery Study (CROSS), and Mamon and Tepper 2 provided an accompanying editorial. CROSS provided definitive evidence of the benefit of preoperative CRT compared with surgery alone for patients with operable esophageal cancer and led to a paradigm shift in practice for many oncologists. 3 However, we question the wisdom of applying these results to all patients with esophageal and junctional cancers, given that the stratified analysis demonstrates a significantly reduced survival advantage for patients with adenocarcinoma compared with squamous cell carcinoma (HR, 0.74 v 0.42). In fact, the benefits of CRT were not statistically significant in either the adenocarcinoma or node-positive subgroups, despite the fact that the vast majority of recruited patients were in these groups. These data suggest that the overall findings of CROSS were strongly driven by the undisputable benefits of CRT in node-negative squamous cell tumors. This argumentisfurtherstrengthenedbythecurrentupdateregardingpatterns of recurrence. ThemultivariableanalysisconfirmsthatthebenefitsofCRTwith respect to local recurrence are markedly greater for patients with squamous cell carcinoma than adenocarcinoma (HR, 0.49; 95% CI, 0.29to0.82).Furthermore,CRTdidnotsignificantlyaffecttheoccurrenceofisolateddistantmetastasesand,incontrasttolocalrecurrence, no breakdown by histologic subtype was provided for distant metastatic disease. We suspect that these distant recurrences may be dominatedbypatientswithadenocarcinoma,inwhichsystemicmetastatic

Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome

Background18Fluor-deoxy-glucose PET-scanning of glycolytic metabolism is being used for staging in many tumors however its impact on prognosis has never been studied in breast cancer. MethodsGlycolytic and hypoxic markers: glucose transporter (GLUT1), carbonic anhydrase IX (CAIX), monocarboxylate transporter 1 and 4 (MCT1, 4), MCT accessory protein basigin and lactate-dehydrogenase A (LDH-A) were assessed by immunohistochemistry in two cohorts of breast cancer comprising 643 node-negative and 127 triple negative breast cancers (TNBC) respectively. ResultsIn the 643 node-negative breast tumor cohort with a median follow-up of 124months, TNBC were the most glycolytic (≈70%), followed by Her-2 (≈50%) and RH-positive cancers (≈30%). Tumoral MCT4 staining (without stromal staining) was a strong independent prognostic factor for metastasis-free survival (HR=0.47, P=0.02) and overall-survival (HR=0.38, P=0.002). These results were confirmed in the independent cohort of 127 cancer patients. ConclusionGlycolytic markers are expressed in all breast tumors with highest expression occurring in TNBC. MCT4, the hypoxia-inducible lactate/H+ symporter demonstrated the strongest deleterious impact on survival. We propose that MCT4 serves as a new prognostic factor in node-negative breast cancer and can perhaps act soon as a theranostic factor considering the current pharmacological development of MCT4 inhibitors.

The Clinical Utility of the Combination of T Stage and Venous Invasion to Predict Survival in Patients Undergoing Surgery for Colorectal Cancer

To examine the clinical utility of improved detection of venous invasion (VI) in patients undergoing potentially curative resection of colorectal cancer. VI is a feature of colorectal cancer (CRC) progression. Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival. A single-center, observational study of pathology variables, including detection of VI by staining for elastica, using 631 stage I to III CRC specimens, collected from 1997 to 2009 (176 analyzed retrospectively and 455 analyzed prospectively), was performed. VI was detected in 56% of patients with CRC. Over a median follow-up period of 73 months, 238 patients died (134 from cancer). On multivariate analysis, VI by elastica staining was associated with a shorter survival duration, independent of other pathology features, in all cases [hazard ratio (HR) = 3.94, 95% confidence interval (CI): 2.33-6.65, P < 0.001] and in node-negative cases (HR = 3.55, 95% CI: 1.81-6.97; P < 0.001). In the absence of elastica-detected VI, with the exception of T stage, no other pathology features were associated with survival time. Therefore, the combination of T stage and VI (TVI) on survival was examined. Five-year cancer mortality could be stratified between 100% and 54% for patients with node-negative tumors and between 100% and 33% for patients with node-positive tumors. In all cases, the TVI had similar predictive value as that of T stage and node status (TNM). In node-negative disease, TVI had superior predictive value. The results of the present study have prompted the development of a novel tumor staging system based on TVI. The TVI has clinical utility, especially in node-negative disease, in predicting outcome following curative resection for CRC.

Adjuvant trastuzumab in the treatment of small HER2-positive tumors: A single institution experience.

e11514 Background: According to St.Gallen Criteria, a high risk node-negative patients will be defined as a patients with negative lymph node involvement and at least one of following factors:tumor size > 2 cm, HR negative, histological and/or nuclear grade 2-3 or age < 35 years.However some patients with HER2 positive cancers develop a recurrence despite small tumor size (< 2 cm) and none of these factors. Six phase III multi-centre trials confirmed the potential benefit of incorporating trastuzumab in adjuvant regimens as a standard treatment. The effectiveness of adjuvant trastuzumab has been demonstrated either for node negative pT1c patients and for diseases at a higher risk. These trial were not able to provide any information regarding the outcome of patients with node negative tumours <1cm. Methods: From Jannuary 2005 to November 2013 in our istitution 101 patients with small Her2 positive and negative nodes breast cancers underwent surgery. 83/101(82,2%) patients had quadrantectomy and local radiotherapy, 18/101( 17,8 %) patients had radical mastectomy. Median age at diagnosis was 50,3 years (range 27- 76). All patients were staged as pT1 N0 M0 : 9/101(8,9 %) patients are pT1a N0, 21/101 (20,8 %) patients pT1b pN0 and 72/101 (71,2 %) patients pT1c pN0. 96/101 (95 %) patients were treated with adjuvant anthracyclines regimens for 4 or 6 cycles followed by one year of trastuzumab ( 52 weeks).70/101 patients follow-up was at least 1 year, median follow up was 46 months ( range 13 months – 108 months). The Left Ejection Ventricular Fraction (LEVF) was assessed at baseline and every three months. Results: 2/70 (1.4%) patients relapsed (one lung metastasis during treatment, one local recurrence 13 months after the last dose). An asymptomatic absolute decrease in LVEF by 10% was reported in five patients. No patients discontinued the treatment. Conclusions: The use of trastuzumab in HER2 positive small tumor seems safe and effective. More data should be available for tumors smaller than 1 cm.

Efficacité et sécurité de la technique de radiothérapie mammaire avec complément d’irradiation concomitant : analyse de 121 cas traités à l’institut de cancérologie de Lorraine

PurposeTo evaluate the safety and efficacy of whole breast irradiation with a concomitant boost. Patients and materialsThis is a retrospective study of 121 patients with node negative T1-T2 breast tumors inferior to 3cm in diameter, previously treated by conservative surgery without chemotherapy. A dose of 50Gy was delivered to the whole breast in 2Gy daily fractions with 5 weekly treatments. A concomitant boost to the lumpectomy site delivered a total of 10Gy in 1Gy fractions twice a week. This would result in an equivalent tumour bed dose (assuming an α/β of 4) of approximately 65Gy in 2Gy fractions. ResultsOver 7 years, 121 patients were treated. The median age was 67 years (range, 46–86 years). Stage distribution was: 115 T1, 6 T2; 116 tumors had positive hormonal receptors, 6 grade SBR3. With a median follow-up of 6 years (range, 1.4–11.4 years), 5-year overall survival was 98.2% (95% confidence interval [CI] 0.95–1), disease-free survival was 100% and local recurrence-free survival 100%. The maximum acute skin toxicity by the end of treatment was grade 2. Cosmetic outcomes were good on the long term. One spontaneous rib fracture was observed 1 year after radiotherapy among 76 patients. ConclusionsThe study shows that whole breast radiation therapy with a concomitant boost is safe and effective for selected patients with low risk of relapse, and gives excellent long term results. This protocol represents a good alternative to longer standard whole breast radiation therapy with sequential boost to the lumpectomy bed.

Gastric Stump Cancer After Distal Gastrectomy for Benign Disease: Clinicopathological Features and Surgical Outcomes

The purpose of the present study was to analyze clinicopathologic features and long-term prognosis of gastric stump cancer (GSC) arising in the remnant stomach 5years or later after partial gastrectomy for benign disease. We reviewed the results of 176 patients resected with curative intent for GSC at 8 Italian centers belonging to the Italian Research Group for Gastric Cancer (GIRCG). The median (range) follow-up time for surviving patients was 71.2 (6-207)months. One hundred forty-six patients were men, the mean age at the time of diagnosis was 69.2years, and the great majority (167 cases) underwent Billroth II reconstruction. R0 resection was achieved in 158 (90%) patients, and in 94 (53%) lymph node dissection was ≥D2. Postoperative mortality and complication rates were 6.2 and 43.2%, respectively. T1 tumor was diagnosed in 45 (25%) cases. Lymph node metastases were evident in 86 patients (49%). Thirteen patients had involvement of the jejunal mesentery nodes (pJN+); five cases were T2-T3 and eight cases were T4. Overall 5-year survival rate was 53.1%. Five-year survival rates were 68.1, 37.8, and 33.1% for pT1, pT2-3, and pT4 tumors, respectively (P=0.001). Five-year survival rate was 56.5% for node-negative tumors (pN0), 32.3% for tumors with nodal metastases without involvement of jejunal mesentery nodes (pN+), and 17.1% for tumors with involvement of jejunal mesentery nodes (pJN+) (P=0.002). Our study suggests that an aggressive surgical approach can achieve a satisfactory outcome in GSC.

Breast cancer nodal metastasis correlates with tumour and lymph node methylation profiles of Caveolin-1 and CXCR4

DNA methylation is the best characterised epigenetic change so far. However, its role in breast cancer metastasis has not as yet been elucidated. The aim of this study was to investigate the differences between the methylation profiles characterising primary tumours and their corresponding positive or negative for metastasis lymph nodes (LN) and correlate these with tumour metastatic potential. Methylation signatures of Caveolin-1, CXCR4, RAR-β, Cyclin D2 and Twist gene promoters were studied in 30 breast cancer primary lesions and their corresponding metastasis-free and tumour-infiltrated LN with Methylation-Specific PCR. CXCR4 and Caveolin-1 expression was further studied by immunohistochemistry. Tumours were typified by methylation of RAR-β and hypermethylation of Cyclin-D2 and Twist gene promoters. Tumour patterns were highly conserved in tumour-infiltrated LN. CXCR4 and Caveolin-1 promoter methylation patterns differentiated between node-negative and metastatic tumours. Nodal metastasis was associated with tumour and lymph node profiles of extended methylation of Caveolin-1 and lack of CXCR4 hypermethylation. Immunodetection studies verified CXCR4 and Caveolin-1 hypermethylation as gene silencing mechanism. Absence of Caveolin-1 expression in stromal cells associated with tumour aggressiveness while strong Caveolin-1 expression in tumour cells correlated with decreased 7-year disease-free survival. Methylation-mediated activation of CXCR4 and inactivation of Caveolin-1 was linked with nodal metastasis while intratumoral Caveolin-1 expression heterogeneity correlated with disease progression. This evidence contributes to the better understanding and, thereby, therapeutic management of breast cancer metastasis process.

Clinical Significance of HER2-Positive and Triple-Negative Status in Small (≤ 1 cm) Node-Negative Breast Cancer

BackgroundData regarding the clinical significance of HER2+ and TN status in patients with small node-negative tumors are limited and conflicting. It remains unclear who, among those with small lesions, might benefit from more aggressive adjuvant therapy. Patients and MethodsWe identified all node-negative breast cancer patients with tumor size ≤ 1 cm diagnosed between January 1, 1995 and December 31, 2008 using our institutional breast service database. Patients were classified according to their receptor status into 3 groups: (1) hormone receptor (HR)-positive (estrogen receptor [ER]- or progesterone receptor [PR]-positive, HER2−); (2) HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization amplification ≥ 2); and (3) TN (ER−, PR−, and HER2−). RFS was calculated using Kaplan-Meier methods. ResultsAmong 656 patients with tumors ≤ 1 cm, 494 (75%) of the patients were HR+, 107 (16%) were HER2+, and 55 (9%) were TN. Median age was 59 years (range, 27-92 years). Median follow-up was 3.5 years. The 5-year RFS rates were 98.2%, 97.1%, and 83.5% in patients with HR+, HER2+, and TN tumors, respectively (P < .001). In multivariate analysis, TN status was associated with worse RFS (hazard ratio, 6.70; 95% confidence interval [CI], 3.02-14.86), and HER2+ was not (hazard ratio, 1.64; 95% CI, 0.73-3.69). ConclusionTN, but not HER2+ status, was associated with worse RFS in patients with T1abN0 tumors, and adjuvant chemotherapy might be considered in patients with TN breast cancer.

Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy

To determine whether tumor grade, molecular subtype and hypoxia predict response to hypofractionated versus standard radiotherapy (RT) following breast-conserving surgery (BCS) for node-negative breast cancer in a randomized controlled trial (RCT). Formalin-fixed paraffin-embedded (FFPE) tumor blocks were available on 989 of 1234 patients enrolled in the Hypofractionation Whole Breast Irradiation (HWBI) Trial. A central pathology review and assessment of tumor grade using the Nottingham grading system was carried out. Tumors were classified by molecular subtype as luminal A, luminal B, HER2 enriched, basal-like or unclassified using a six-biomarker panel; ER, PR, HER-2, Ki67, CK5/6 and EGFR. Tumors were also classified as hypoxic based on the expression of HIF1α, CAIX or GLUT-1. The primary end point was local recurrence (LR). Median follow-up was 12 years. In the multivariable Cox model, molecular subtype was the only factor predictive of LR, the 10-year cumulative incidence was 4.5% for luminal A and basal-like, 7.9% for luminal B and 16.9% for HER-2 enriched tumors (P < 0.01). Tumor grade, molecular subtype or hypoxia did not predict response to hypofractionation. In women enrolled in the HWBI trial following BCS tumor molecular subtype predicted LR. However tumor grade, molecular subtype and hypoxia did not predict response to hypofractionation suggesting that patients with node-negative breast tumors of all grades and molecular subtypes may be safely treated with hypofractionated RT regimens.

Variability in immune infiltrates and HLA expression in cholangiocarcinoma.

230 Background: Cholangiocarcinoma continues to have a dismal prognosis. The lack of effective therapy prompted us to determine whether patients develop an immune response against their own tumors. The aim of this study is to evaluate the CD8 infiltrate and expression of HLA class I antigen processing machinery (APM) components in cholangiocarcinoma. The HLA class I antigen processing machinery (APM) components play a crucial role in expression of HLA class I tumor antigen derived peptide complexes. These complexes mediate the recognition of tumor cells by cognate T cells. Defects in the expression of HLA class I APM components by tumor cells suggests that the infiltrating lymphocytes impose selective pressure on tumor cells. This selective pressure would facilitate the outgrowth of tumors by escaping T cell recognition. Methods: Retrospective review of clinicopathologic factors was performed for 18 peripheral cholangiocarcinomas. Formalin fixed, paraffin embedded tumors were evaluated for the content of lymphocyte infiltrates and for the expression of HLA class I APM components. Results: Eighteen patients underwent a partial hepatectomy for peripheral cholangiocarcinoma of whom 10 were female. Median age was 63yo. The majority of patients had node negative tumors (10/12). All tumors had lymphocytic infiltration. Median number of lymphocytes in the fibrous septae between tumor lobules was 42 CD8 T cells per 10 high power field, but only 4 CD8 T cells within tumor lobules. HLA class I APM components was defective and not detected in three tumors, all of which were poorly differentiated. HLA expression was down regulated in 9 tumors. HLA expression was in normal range in the remaining 6 tumors. Median overall survival has not been reached. Conclusions: Lymphocytic infiltrates were seen in all resected cholangiocarcinoma specimens. The loss of HLA class I APM component expression in cholangiocarcinoma suggests that infiltrating lymphocytes reflect a patient’s immune response to his/her tumor. This information provides a sound rationale to consider immunotherapy in the treatment of cholangiocarcinoma, specifically with antibodies to check point molecules which enhance patients’ immune response against his own tumors.

The role of adjuvant radiation therapy in T4 nonrectal colon cancers.

553 Background: The standard treatment for non-metastatic locally advanced (T4M0) non-rectal colon cancer is surgical resection followed by adjuvant chemotherapy. There is strong rational for the use of post-operative radiation therapy (RT) in T4 tumors since negative margins are difficult to obtain. Despite promising single institutional studies, a phase III clinical trial closed early due to poor accrual. The efficacy of adjuvant RT in these patients remains unknown. We hypothesized that patients at lower risk of micro-metastases would benefit most from aggressive local treatment. Methods: Cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Inclusion criteria: T4-anyN-M0 non-rectal colon cancers, diagnosed between 1988 and 2010. Exclusion criteria: rectal tumors and cases lacking staging information. Endpoints: overall survival (OS) and cancer-specific survival. Analyses were based on the Kaplan-Meier method and Cox proportional hazard model. Results: A total of 36,260 patients with T4 colon cancer were identified. Due to changes in the use of systemic adjuvant therapies, an initial analysis was performed to determine effect of adjuvant RT by year of diagnosis. Prior to 2003, adjuvant RT provided no significant improvement in OS. However, between 2003 and 2010, adjuvant RT improved OS by 8 months, from 48 to 56 months (HR: 0.83, p = 0.001). Within this latter period, adjuvant RT improved OS in three subsets of the population: in patients without nodal involvement (N0) (HR: 0.79, p = 0.009); in patients with primary tumor in the sigmoid colon (HR: 0.79, p=0.007); in patients with primary tumor size of 6cm or greater (HR: 0.74, p &lt; 0.001). On multivariate analysis, the following categories remained significant: N stage, tumor grade, year of diagnosis, gender, primary site, and radiation therapy. Conclusions: Some patients with T4 non-rectal colon cancer appear to benefit from adjuvant RT after surgical resection of the primary tumor, especially node-negative tumors located within the sigmoid colon, larger than 6cm in diameter. This benefit has become more evident since the introduction of more effective adjuvant chemotherapy. Our conclusions require verification in a prospective study.

Is There a Role for Postmastectomy Radiation Therapy After Complete Pathologic Response to Neoadjuvant Chemotherapy?

Patients with locally advanced breast cancer who undergo neoadjuvant chemotherapy and who are found to have a pathologic complete response (pCR) at the time of mastectomy pose a unique challenge to the radiation oncologist. Whereas patients with node-negative disease and small primary tumors treated immediately by mastectomy do not generally require postmastectomy radiation (PMRT), radiation indications are unclear for patients who present initially with more advanced disease and become node-negative after chemotherapy. Consequently, guidelines and patterns of practice for PMRT after neoadjuvant vary substantially among institutions and clinicians both nationally and internationally. Although some retrospective data suggest that patients with a pCR are at low risk of local failure and may not require adjuvant PMRT, there are conflicting data suggesting a role for PMRT, depending on the initial clinical stage at presentation. A national multi-institutional trial is currently investigating this question.

Key architectural changes in tumor-negative lymph nodes from metastatic-free oral cancer patients are valuable prognostic factors

Regional lymph node (LN) metastasis in oral cancer patients is the most significant grave prognostic factor. We evaluated the relationship between clinical outcomes and different histopathological changes in tumor-negative LNs (LN0) selected from neck dissections without metastatic disease (pN0). A total of 435 LN0 selected from pN0 neck dissections (up to three nodes in each level) were scored for histopathological parameters of LN areas, capsule thickness, subcapsular and medullary sinus ectasia, lobular architecture and percent of cortical reactive follicles. These were compared to 328 LN0 selected from neck dissections with metastases (pN+) after exclusion of metastatic LNs. Data were presented by maximum scores of each parameter in I-III (close) and in IV-V (distant) levels. Limited data from level V and regression analyses inferred that the values in level IV represented the worst changes for most patients. Cox proportional hazard regression on each parameter in close and distant levels demonstrated that capsule thickness, number of lobules and percent of reactive follicles were significantly associated with time to death from disease. The higher the change in distant levels, the shorter the time to death, while the higher the change in close levels (given a stable change in distant levels), the longer the time to death. After adjustment for gender, age and location, only the effect of the percent of reactive follicles retained their significant effect. Logistic regression of metastases demonstrated that all parameters except for percent of reactive follicles were significantly associated with risk of metastases, with differences between close and distant levels similar to those found for time to death. After adjustment for gender, age and location, only the area and number of lobes retained their significance. The findings of this study suggested that selective histopathological changes in tumor-negative LNs in metastatic-free patients provide new valuable prognostic parameters.

Skin-Sparing Mastectomy and Breast Reconstruction: An Update for Clinical Practice

Aim: To provide an up-to-date review of the literature on skin-sparing mastectomy (SSM) for breast cancer (BC). The article also reviews the oncological safety, effects of radiotherapy (RT) on immediate breast reconstruction (IBR), the indications for preserving the nipple-areola complex (NAC) and the emerging role of allogenic grafts as adjuncts to implant in IBR. Methods: Review of the English literature from 1965 to 2013 was carried out using Medline and PubMed research engines. Results: SSM is oncologically safe in appropriately selected cases of invasive breast cancer (IBC) and ductal carcinoma in-situ (DCIS) including IBC 5 cm, multi-centric tumours, DCIS and for risk-reduction surgery. Inflammatory breast cancer and tumours with extensive skin involvement represent contra-indications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy (PMRT) do not preclude SSM with IBR, however the aesthetic outcome may be compromised by radiation. Preservation of the nipple-areola complex (NAC) has aesthetic and psychological benefits and is safe for peripherally located node negative unifocal tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be performed when NAC preservation is considered. The advent of acellular dermal matrix has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetics outcome. There is no sufficient evidence to support the role of endoscopic mastectomy in clinical practice. Conclusion: Numerous retrospective and prospective studies show that SSM is oncolgically safe in appropriately selected cases and is aesthetically superior to non-SSM mastectomy. New tech-niques such as the use of acellular dermal matrix (ADM) and cell-assisted fat transfer have increased the use of implants for volume replacement following SSM. In the absence of randomized clinical trials, an updated systematic meta-analysis of published studies is required in order to consolidate the evidence.

Prognosis of vulval cancer with lymph node status and size of primary lesion: A survival study

Introduction:Squamous cell cancer of the vulva is a rare disease with an annual incidence of two to three per 100,000 women. Lymph node metastasis is the most important prognostic factor for the recurrence and survival in vulval carcinoma.Materials and Methods:It is a retrospective study of 18 cases, operated in our institute from 2006 to 2009 and followed up till July, 2012. These patients were divided into two group of node positive and node negative and compared for recurrence and survival.Result:Ten patients had lymph node metastasis and eight had no lymph node metastasis. Recurrence rate was 40% and 12.5% in node positive and negative groups, respectively. Adjuvant radiation when given to node negative bulky tumor showed no recurrence compared to one out of two in the non-irradiated group. Survival was only 25% in node positive recurrent cases.Conclusion:Lymph node positivity added a great risk for future recurrence. Prophylactic radiation in node negative, bulky tumor is helpful.

Evolving role of skin sparing mastectomy.

Skin sparing mastectomy (SSM) can facilitate immediate breast reconstruction and is associated with an excellent aesthetic result. The procedure is safe in selected cases; including invasive tumours < 5 cm, multi-centric tumours, ductal carcinoma in situ and for risk-reduction surgery. Inflammatory breast cancers and tumours with extensive involvement of the skin represent contra-indications to SSM due to an unacceptable risk of local recurrence. Prior breast irradiation or the need for post-mastectomy radiotherapy do not preclude SSM, however the aesthetic outcome may be compromised. Preservation of the nipple areola complex is safe for peripherally located node negative tumours. An intraoperative frozen section protocol for the retro-areolar tissue should be considered in these cases. The advent of acellular tissue matrix systems has enhanced the scope of implant-based immediate reconstruction following SSM. Cell-assisted fat transfer is emerging as a promising technique to optimise the aesthetic outcome.

Abstract P6-06-46: Treatment decisions and five year outcomes of the oncotype Dx test: An independent assessment

Abstract INTRODUCTION: Oncotype DX (ODx) was validated to provide prognostic information in ER+ lymph node negative tumors. The work of Paik et al. (JCO 2006 23:3737) has provided evidence of predictive power of ODx for chemotherapy, but there is contrary literature in this regard (Ionnadis JP Oncologist 2007, 12: 301-11; NICE Guideline March 2013 http://guidance.nice.org.uk/DT4). The specific aims of our institutional study are to determine (1) how ODx influenced treatment decisions and (2) the outcomes of patients who had ODx. METHODS: Tumor registry follow-up information was supplied for 580 patients who had ODx and follow-up (mean/median 60/63 months). RESULTS: (Table 1) Distribution of RS was 40% intermediate (232/580), 15% high RS (87/580) and 45% (261/580) low RS. Hormonal therapy was recommended to 96% (558 of 580), but refused by 3% (16 of 580) and for 1% data was unavailable. In the high RS group, chemo was recommended to 90% (79 of 87), of which 6 (8%) refused. In the intermediate RS group, chemo was recommended to 49% of the patients of which 20 (18% of recommended) refused. In the low RS group, chemo was recommended to 12% of the patients of which 8 (26% of recommended) refused. Most chemotherapy treatment decisions made at our institution were based on oncotype DX. High RS group recurrence was 9% (7 of 87) of which 2 patients died. Of these 7 patients, 3 did not receive chemotherapy (2 were recommended but refused). The recurrence rate in the intermediate RS group was 6.5% (14 of 232) of which 3 patients died. Of these 14 patients, 8 did not receive chemotherapy based on clinician's judgment. The recurrence rate in the low RS group was 1% (3 of 261) and there were no deaths due to breast cancer. Of these 3 cases, one received chemotherapy. Oncotype DX Type of Recurrence vs Recurrence ScoresType RecurrenceHigh RSIntermediate RSLow RSTotalLocoregional49114(Scores)(35,38,47,63)(19,20,20,23,24,26,26,27,29)(16) Distant2529(Scores)(31,61)(19,19,22,29,30)(2,11) Local or Distant1 1Total714324 Conclusion: (1) The oncotype DX recurrence score is prognostic when low risk and high risk categories are considered. (2)The large number (40%) of intermediate RS appears to be a prognostic limitation of the test. (3) Of patients that recurred, (50%) received chemotherapy and were somewhat equally distributed between the high RS and the intermediate RS categories. Further follow-up of this cohort should address concerns of clinical utility of the Oncotype Dx test, especially for the intermediate RS category. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-46.

Abstract P2-16-11: Impact of adjuvant trastuzumab (T) with chemotherapy on breast cancer specific and cardiac outcomes in older women with small, node-negative HER2-positive breast cancer

Abstract Introduction: For women with high risk early breast cancer that overexpresses HER2, the role of adjuvant T with chemotherapy is well established. Although the benefits of this approach in women with small, node negative tumors are less well defined, we previously published a retrospective sequential cohort study that suggested that T with chemotherapy is active in this setting. However there are few data about the safety and efficacy of adjuvant T in older women with small, node negative HER2+ breast cancer. Thus, this we conducted a retrospective study of breast cancer specific and cardiac outcomes for this subset. Methods: From our previously reported dataset, we identified women &amp;gt; 60y with &amp;lt;2 cm, node-negative HER2+ breast cancer. We identified a “no-T” cohort of 32 women diagnosed Jan ‘02 - May ‘05 and a “T” cohort of 39 patients diagnosed May ‘05 - Dec ‘08. Electronic medical records were reviewed to examine risk factors and incidence of cardiotoxicity as well as patient outcomes including distant disease-free survival (DDFS) and overall survival (OS). Results: Women in the two cohorts had similar baseline characteristics including cardiac risk factors (Table 1). There were no cardiac events in the no-T group. In the T group, 3 patients discontinued T due to a cardiac event: 1 with asymptomatic decline in ejection fraction (EF), 1 with atrial fibrillation and dyspnea, and 1 with symptomatic EF decline associated with myocardial infarct and valvular disease. Patients in both cohorts had excellent disease control at a median follow up of 9y and 6y for the no-T and T cohorts respectively. The 3y DDFS numerically favors the T cohort, the confidence intervals are broad and overlapping (Table 1). There were no detectable differences in OS between groups. In our previous report (not selected for age), DDFS at 3yrs was 95% (90-99) and 100% in the no-T (N = 106) and T (N = 155) cohorts respectively. Conclusion: In this small retrospective study, older women with small, node negative HER2+ breast cancers had excellent disease control and a low risk of cardiotoxicity. The possible benefits of T in this setting are consistent with prior reports uncontrolled for age. Table 1 No Trastuzumab N = 32 N (%)Trastuzumab N = 39 N (%)Tumor Size (cm), median (range)1.4 (0.1-2.0)1.3 (0.5-2.0)Multifocal Disease6 (19)4 (10)Grade 324 (75)33 (85)ER Positive20 (63)20 (51)Age, median (range)66 (60-85)65 (60-82)BMI, median (range)24.7 (18.2-34.2)27.3 (18.2-47.1)Chemotherapy16 (50)39 (100)Radiotherapy23 (72)25 (64)Hypercholesterolemia11 (34)18 (46)Hypertension12 (38)13 (33)3yr DDFS (95% CI)91% (74-97)97% (83-100)3yr OS (95% CI)97% (80-100)97% (83-100) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-16-11.