The treatment outcome of patients undergoing breast-conserving therapy: the clinical role of postoperative radiotherapy

Background  Treatment outcome was evaluated in patients who underwent breast-conserving therapy and tangential irradiation. After verifying background factors including systemic therapy, the clinical efficacy of postoperative irradiation was investigated. Method  There were 708 study subjects, all of whom had early breast cancer treated between 1992 and 2002. The median follow-up period was 83 months. After breast-conserving surgery, in patients with negative surgical margins, only tangential irradiation at 48 Gy/24 fr was performed. In contrast, in those with positive surgical margins, 10 Gy of radiation boost to the tumor bed with electrons was administered after tangential irradiation with 50 Gy/25 fr. Treatment outcome was analyzed using the Kaplan–Meier method and Cox’s proportional hazards regression model. Results  The disease-free survival and no-recurrence rates within the ipsilateral breast after 5 years were 93.4 and 97.2%, respectively. Risk factors for recurrence within the ipsilateral breast included younger age of patient, the number of positive lymph nodes, and no endocrine therapy. However, the surgical margin was not a risk factor. Risk factors for relapse outwith the ipsilateral breast included younger age, the number of positive lymph nodes, and recurrence within the ipsilateral breast. Conclusions  From our analysis of 708 Japanese women who received breast-conserving therapy, which can be regarded as a standard method in Japan, the treatment outcome was compatible with previous reports from other countries. Presented in part at the 19th meeting of the Japanese Society for Therapeutic Radiation Oncology (JASTRO), 23–25 November 2006, Sendai, Japan.     

Breast cancer subpopulation with high risk of internal mammary lymph nodes metastasis: analysis of 2,269 Chinese breast cancer patients treated with extended radical mastectomy

Purpose The selective treatment of internal mammary lymph nodes (IMNs) in breast cancer is controversial. The purpose of this research was to determine the subpopulation patients with high risk of internal mammary lymph nodes metastasis who received extended radical mastectomy without any preoperative treatment from 1956 to 2003 in China. Patients and methods 1,679 Chinese patients were underwent extended radical mastectomy (ERM) between 1956 and 2003. Four individual variables were selected (tumor site, tumor size, the number of ALNs involvement, patient age),then classified by following standards: tumor site(lateral, central, medial),tumor size(T1:≤2 cm; T2:2 < T ≤ 5 cm, T3:>5 cm), ALNs(0,1–3,4–6, ≥7), age(≤35 y, 36–50 y, >50 y). Chi-square and binary logistic regression were used to analysis relationship of these variable and IMMs. Results The four individual variables were significantly associated with IMNs metastasis using univariate analysis. However, three individual variables except for tumor size independently impact the IMNs metastasis using multivariate analysis. The incidence of IMNs metastasis in patients with 4–6 and ≥7 positive ALNs was 28.1%, 41.5%. Within subgroup patients with medial tumor and positive ALNs, the incidence of IMNs metastasis was 23.6% for patients with 1–3 positive ALNs, and 47.5% for 4–6 positive ALNs, 38.7% for patients with ≥7 positive ALNs. The incidence of IMNs metastasis was 25.4% for patients with T3 tumor and younger than 35 y. Conclusion Patients with following conditions had high risk of IMNS metastasis: (1) patients with 4 or more positive ALNs. (2) patients with medial tumor and positive ALNs.(3) patients with T3 tumor and younger than 35 y. (4) patients with T2 tumor and positive ALNs.(5) patients with T2 tumor and medial tumor .The incidences of IMNS metastasis for those patients were more than 20%.     

Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence.

PURPOSE: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy. PATIENTS AND METHODS: The study population comprised 533 patients with International Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of invasive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed. Median follow-up time was 127 months. RESULTS: At 8 years, patients with close margins and those with negative margins both had a rate of local recurrence (LR) of 7%. Patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%. In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease. Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%). CONCLUSION: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy.     

A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger

Introduction: Indications for postmastectomy radiation include primary tumor size ≥5 cm and/or ≥4 positive axillary nodes. In clinical practice, patients with a close or positive margin after mastectomy are also often treated with postmastectomy radiation. However, there is little data regarding the risk of a chest wall recurrence in patients with close or positive margins who otherwise would be considered low risk (tumor size <5 cm and/or 0–3 positive nodes). To address this issue, we assessed the risk of a chest wall recurrence in women with Stage I–II breast cancer who underwent mastectomy and were found to have primary tumor size <5 cm and 0–3 positive nodes with a close or positive deep margin.Methods and Materials: The pathologic reports from 789 patients treated by mastectomy between 1985 and 1994 at our institution were retrospectively reviewed. Of these, 136 (17%) had tumor within 1 cm of the deep resection margin. The study population consists of 34 of these patients with close or positive margins whose primary tumor size was <5 cm with 0–3 positive axillary nodes and who received no postoperative radiation. The median age was 43 years (range 29–76). Of these, 44% had T1 tumors and 56% T2 tumors. Pathologic axillary nodal status was negative in 65% and positive in 35%. The median number of positive nodes was 1. The deep margin was positive in 2 patients, ≤2 mm in 17 patients, 2.1–4 mm in 7 patients and 4.1–6 mm in 8 patients. Of the 34 patients, 67% received adjuvant chemotherapy ± tamoxifen and 21% received tamoxifen alone. The median follow-up was 59 months (range 7–143).Results: There were 5 chest wall recurrences at a median interval of 26 months (range 7–127). One was an isolated first failure, one occurred concurrent with an axillary recurrence, and three were associated with distant metastases. The 5- and 8-year cumulative incidences of a chest wall recurrence were 9% and 18%. Patient age correlated with the cumulative incidence of chest wall recurrence at 8 years; age ≤50 years had a rate of 28% vs. 0% for age >50 (p = 0.04). There was no correlation with chest wall failure and number of positive nodes, ER status, lymphovascular invasion, location of primary, grade, family history, or type of tumor close to the margin. Of 5 chest wall failures, 4 were in patients who had received adjuvant systemic chemotherapy ± tamoxifen. Chest wall failures occurred in 1 patient with a positive deep margin, 3 patients with margins within 2 mm, and 1 patient with a margin of 5 mm. The estimated cumulative incidence probability of chest wall recurrence at 8 years by margin proximity was 24% ≤ 2 mm vs. 7% 2.1–6 mm (p = 0.36), and by clinical size 24% for T2 tumors vs. 7% for T1 (p = 0.98).Conclusions: A close or positive margin is uncommon (≤5%) after mastectomy in patients with tumor size <5 cm and 0–3 positive axillary nodes but, when present, it appears to be in a younger patient population. The subgroup of patients aged 50 or younger with clinical T1–T2 tumor size and 0–3 positive nodes who have a close (≤5 mm) or positive mastectomy margin are at high risk (28% at 8 years) for chest wall recurrence regardless of adjuvant systemic therapy and, therefore, should be considered for postmastectomy radiation.     

Prognostic Factors for Patients with FIGO Stage-IB Cervical Squamous Cell Carcinoma：Does the Tumor Size（≤4 cm or〉4 cm）Really Matter？

OBJECTIVE To investigate the factors that can accurately predict the prognosis for patients with FIGO stage-IB cervical squamous cell carcinoma treated with radical surgery. METHODS A retrospective analysis of clinical data from 174 cases of FIGO Stage-IB cervical squamous cell carcinoma treated in our institute was conducted. RESULTS The 5-year overal disease-free survival of the patients was 79.4%and the recurrence rate was 16.7%.Seventy-five percent of the 60 patients with a tumor>4 cm and 28.1%of the 114 patients with a tumor≤4 cm received preoperative radiotherapy,resuting in a significant difference be- tween the two groups(P<0.001).The 5-year disease-free survival rate for the groups with a tumor≤4 cm without and with preoperative radiotherapy, and with a tumor>4 cm without and with preoperative radiation therapy were 80.5%,85.2%,69.3%and 77.1%,respectively.There was no significant dif- ference between any of the groups(P>0.05).A univariate analysis showed that pelvic node metastasis,a positive parametrial surgical margin and post- operative adjuvant therapy were al significantly correlated with the 5-year disease-free survivals(P<0.05).Multivariate analysis revealed that pelvic node metastasis(P=0.004)and a positive parametrial surgical margin(P= 0.040)were independent factors that influenced the prognosis.The 5-year disease-free survivals for the cases with a tumor≤4 cm and>4 cm were 57.4%and 44.7%respectively in the high-risk group(patients with pelvic lymphatic metastasis and/or positive parametrial surgical margin)(P=0.575) and the recurrence ratio was 7/18 and 6/14 for the cases of the two tumor sizes in the same risk group.There was no significant difference between the two groups(P=0.821).The 5-year disease-free survivals for the cases with a tumor≤4 cm and>4 cm were 86.5%and 82.9%respectively in the low-risk group(patients without pelvic lymph-node metastasis and/or positive para- metrial surgical margin),respectively(P>0.05)and the recurrence ratio was 9/95 and 7/47 for the cases of the two tumor sizes in the same risk group. There was no significant difference between the two groups(P>0.05). CONCLUSIONS For FIGO Stage-IB cervical squamous cel carcinoma patients with radical surgery as the major means of treatment,the features of pelvic lymph-node metastasis and a positive parametrial surgical margin are independent factors that influence the prognosis.The tumor size can not be used as a criterion for predicting the prognosis.     

Progesterone receptor is a significant factor associated with clinical outcomes and effect of adjuvant tamoxifen therapy in breast cancer patients

Estrogen receptor status in breast cancer is associated with response to hormonal therapy and clinical outcome. The additional value of progesterone receptor (PR) has remained controversial. We examine the value of PR for prognosis and response to tamoxifen on a population-based series of 4,046 invasive early stage breast cancer patients. Clinical information for age at diagnosis, stage, pathology, treatment and outcome was assembled for the study cohort; the median follow-up was 12.4 years. PR status was determined by immunohistochemistry using a rabbit monoclonal antibody on tissue microarrays built from breast tumor surgical excisions. Survival analyses, Kaplan–Meier functions and Cox proportional hazards regression models were applied to assess the associations between PR and breast cancer specific survival. Progesterone receptor was positive in 51% of all cases and 67% of estrogen receptor positive (ER+) cases. Survival analyses for both the whole cohort and ER+ cases given tamoxifen therapy showed that patients with PR+ tumors had 24% higher relative probability for breast cancer specific survival as compared to PR− patients, adjusted for ER, HER2, age at diagnosis, grade, tumor size, lymph node status and lymphovascular invasion covariates. Higher PR expression showed stronger association with patient survival. Log-likelihood ratio tests of multivariate Cox proportional hazards regression models demonstrated that PR was an independent statistically significant factor for breast cancer specific survival in both the whole cohort and among ER+ cases treated with tamoxifen. PR adds significant prognostic value in breast cancer beyond that obtained with estrogen receptor alone.     

Prognostic impact of isolated tumor cells in breast cancer axillary nodes: single tumor cell(s) versus tumor cell cluster(s) and microanatomic location

In breast cancer, it has been shown that pN0(i+) and pN1mi have a comparable negative impact on disease-free survival, compared with pN0. However, pN0(i+) is considered to be a heterogeneous group. We determined the effect of metastatic size and microanatomic location within the pN0(i+) group on breast cancer recurrence. We included all Dutch breast cancer patients diagnosed in 1998–2005 with favorable primary tumor characteristics and a final nodal status of pN0(i+). For this analysis, only patients without adjuvant systemic therapy were eligible (n = 513). Presence of single tumor cells versus cell clusters, metastatic size and microanatomic location were recorded. Primary endpoint was disease-free survival. Analyses were adjusted for age at diagnosis, tumor size, tumor grade, axillary treatment and hormone receptor status. The 5-year disease-free survival of patients with single tumor cell(s) (n = 93) was 78.6% and with tumor cell cluster(s) (n = 404) 77.1%. The hazard ratio for disease events was 1.05 (95% CI 0.63–1.76) for cell cluster(s) compared with single cell(s). In a Cox regression model, doubling of metastatic tumor size corresponded to a hazard ratio of 1.21 (95% CI 1.02–1.43). The adjusted hazard ratio was 0.90 (95% CI 0.54–1.50) for parenchymal (n = 112) versus sinusoidal location (n = 395). Single tumor cells bear similar prognostic information as small tumor cell clusters, even though results do suggest that within the pN0(i+) group, increasing size of nodal involvement is associated with reduced survival. Microanatomic location does not seem to have prognostic relevance.     

Margin status and the risk of local recurrence after breast-conserving treatment of lobular breast cancer

Background Invasive lobular breast carcinoma is known for its multicentricity and is associated with a higher incidence of incomplete excision after breast-conserving therapy. The aim of the study was to examine the influence of positive surgical margins on the local recurrence rate in patients diagnosed with invasive lobular cancer and treated with breast-conserving therapy. Methods All 416 women diagnosed with invasive lobular breast cancer and undergoing breast-conserving treatment between 1995 and 2002 were selected from the population-based Eindhoven Cancer Registry. Their medical charts were reviewed and detailed information was collected. Results The risk of margin involvement was 29% after the first operation and 17% when taking into account the final margin status of the patients undergoing re-excision. During follow-up, 18 patients developed a local recurrence. The 5 year actuarial risk of developing a local recurrence was 3.5% (95% confidence interval 2.5–4.5) and the 8 year risk was 6.4% (95% confidence interval 4.7–8.0). There was no influence of positive surgical margins on the risk of local recurrence, neither in the univariate analysis nor after adjustment for age, tumour size, nodal status and adjuvant systemic treatment. Conclusion Patients with invasive lobular cancer, treated with breast-conservation, have a low risk of local recurrence, despite their high risk of having a microscopically incomplete excision of the tumour.     

Axillary nodal involvement by primary tumor features in early breast cancer: an analysis of 2600 patients

Primary tumor characteristics, which are readily available to all clinicians, may aid in selecting the optimal adjuvant therapy for patients with breast cancer (BC). Herein, we investigated the relationship between tumor size, hormone receptor and HER2 status, Ki67 and age with axillary lymph node metastases (ALNM) in early-BC patients. We analyzed data on consecutive 2600 early-BC cases collected in the registry of Fondazione IRCC Istituto Nazionale dei Tumori, Milano, Italy. Correlation between Ki67 and primary tumor size (T-size) was calculated by Spearman’s rank correlation coefficient. Association of ALNM with Ki67 and other tumor characteristics was investigated by logistic regression. Adjusted odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated in all cases, and separately analyzed according to age, T-size and BC subtype. Large tumor size strongly associated to ALNM, with an adjusted odds ratio (OR) for each 5-mm increase of 1.32 (95% CI 1.24–1.41), except for triple-negative BC (TNBC) cases. In tumors =10 mm, without lymphovascular invasion, representing the strongest predictor of ALNM (OR 6.09, 95% CI 4.93–7.53), Ki67 resulted particularly informative, with a fourfold increased odds of ALNM for values > 30%. These results raise the question whether axillary node status is redundant in cases with exceptionally good features, i.e., small tumors with low Ki67, or in those candidate to adjuvant systemic treatment/radiotherapy anyway including TNBC, and support the incorporation of primary BC tumor characteristics as stratification factors in ongoing trials aiming at de-escalating axillary surgical procedures.     

Neoadjuvant Chemotherapy: Does It Have Benefits for the Surgeon in the Treatment of Advanced Squamous Cell Cancer of the Oral Cavity?

The purpose of this clinicopathological study was to evaluate the effects and efficiency of combined neoadjuvant chemotherapy related to surgical margin. 100 consecutively treated squamous cell cancer patients receiving a combined neoadjuvant therapy were selected (Bleomycin—Vincristin—Methotrexate (BVM) or BVM + Mitolactol or BVM + Cisplatin). After three courses of chemotherapy, the patients were operated on. The largest diameter of the primary tumors was compared before and after chemotherapy. In the surgical specimen, the involvement of surgical margin was assessed. The largest diameter before chemotherapy was: T2 30%; T3 55%; T4A 15%. After chemotherapy, the rest tumor was assessed in the surgical specimen as: no rest 11%; <2 cm 57%; 2–4 cm 28%; 4–6 cm 4%. The no rest and <2 cm (optimal operability) tumor was observed in T2: 94%; in T3: 73%; in the T4A: 0%. Severe side effects (Grade III–IV) were not observed. There was a significant decrease in size (P < 0.0001). Of the 100 surgical specimens, 83% had clear-, 9% close- and 8% involved margins. From T4A, there was a 40% (6 patients) involved margin. Based on the significantly better size and operability of primary T2-3, the mild side effects and the high (83%) percentage of clear surgical margins, that is better than other (without preoperative chemotherapy) results, sought the use of chemotherapy is recommended before surgery. Due to the 40% involved margin, we don’t suggest surgery in T4A.     

Margin status and the risk of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy

We sought to assess whether a close surgical margin (>0 and <2 mm) after breast-conserving therapy (BCT) confers an increased risk of local recurrence (LR) compared with a widely negative margin (≥2 mm). We studied 906 women with early-stage invasive breast cancer treated with BCT between January 1998 and October 2006; 91 % received adjuvant systemic therapy. Margins were coded as: (1) widely negative (n = 729), (2) close (n = 85), or (3) close (n = 84)/positive (n = 8) but having no additional tissue to remove according to the surgeon. Cumulative incidence of LR and distant failure (DF) were calculated using the Kaplan–Meier method. Gray’s competing-risk regression assessed the effect of margin status on LR and Cox proportional hazards regression assessed the effect on DF, controlling for biologic subtype, age, and number of positive lymph nodes (LNs). Three hundred seventy-seven patients (41.6 %) underwent surgical re-excision, of which 63.5 % had no residual disease. With a median follow-up of 87.5 months, the 5-year cumulative incidence of LR was 2.5 %. The 5-year cumulative incidence of LR by margin status was 2.3 % (95 % CI 1.4–3.8 %) for widely negative, 0 % for close, and 6.4 % (95 % CI 2.7–14.6 %) for no additional tissue, p = 0.3. On multivariate analysis, margin status was not associated with LR; however, triple-negative subtype (AHR 3.7; 95 % CI 1.6–8.8; p = 0.003) and increasing number of positive LNs (AHR 1.6; 95 % CI 1.1–2.3; p = 0.025) were associated. In an era of routine adjuvant systemic therapy, close surgical margins and maximally resected close/positive margins were not associated with an increased risk of LR compared to widely negative margins. Additional studies are needed to confirm this finding.     

Influence of margin status and radiation on recurrence after radical hysterectomy in Stage IB cervical cancer

PURPOSE: To examine the relationship between margin status and local recurrence (LR) or any recurrence after radical hysterectomy (RH) in women treated with or without radiotherapy (RT) for Stage IB cervical carcinoma. METHODS AND MATERIALS: This study included 284 patients after RH with assessable margins between 1980 and 2000. Each margin was scored as negative (> or =1 cm), close (>0 and <1 cm), or positive. The outcomes measured were any recurrence, LR, and relapse-free survival. Results: The crude rate for any recurrence was 11%, 20%, and 38% for patients with negative, close, and positive margins, respectively. The crude rate for LR was 10%, 11%, and 38%, respectively. Postoperative RT decreased the rate of LR from 10% to 0% for negative, 17% to 0% for close, and 50% to 25% for positive margins. The significant predictors of decreased relapse-free survival on univariate analysis were the depth of tumor invasion (hazard ratio [HR] 2.14/cm increase, p = 0.007), positive margins (HR 3.92, p = 0.02), tumor size (HR 1.3/cm increase, p = 0.02), lymphovascular invasion (HR 2.19, p = 0.03), and margin status (HR 0.002/increasing millimeter from cancer for those with close margins, p = 0.03). Long-term side effects occurred in 8% after RH and 19% after RH and RT. CONCLUSION: The use of postoperative RT may decrease the risk of LR in patients with close paracervical margins. Patients with other adverse prognostic factors and close margins may also benefit from the use of postoperative RT. However, RT after RH may increase the risk of long-term side effects.     

Survival in 12,653 breast cancer patients with extensive axillary lymph node metastasis in the anthracycline era

Institutional data are conflicting regarding the prognosis of breast cancer patients with extensive (≥10) axillary lymph node (ALN) metastases. We hypothesized that overall survival (OS) and disease specific survival (DSS) improved after the introduction of anthracycline-based therapy in 1997. We used the Surveillance, Epidemiology, and End results (SEER) database to identify breast cancer patients with ≥10 ALN metastases diagnosed between 1988 and 2004. Patients were categorized according to whether they were diagnosed prior to the FDA approval of anthracyclines (pre-anthracycline era, pre-AE) or after approval (post-anthracycline era, post-AE). Univariate analyses of OS and DSS were performed using the Kaplan–Meier method and differences assessed via the log rank test. Anthracycline era as an independent predictor of OS and DSS was evaluated using Cox proportional hazards models with patient age, hormone receptor status, tumor size, use of radiation therapy, and number of metastatic ALNs as covariates. Entry criteria were met by 12,653 patients. Of these, 5,655 (44.7%) and 6,998 (55.3%) were treated in the pre-AE and post-AE, respectively. On univariate analysis, post-AE patients experienced significantly improved rates of OS (P < 0.001) and DSS (P < 0.001) relative to pre-AE patients. On multivariate analysis, treatment in the post-AE favorably influenced both OS (Hazard Ratio [HR] 0.90, 95% Confidence Interval [CI] 0.84–0.96) and DSS (HR 0.84, CI 0.79–0.91). Both OS and DSS are poor in patients with extensive ALN metastases. Patients with advanced breast cancer treated in the post-AE demonstrated superior OS and DSS.     

Breast cancer and spider telangiectasias at diagnosis and its relation to histopathology and prognosis: a population-based study

Angiogenesis is one of the hallmarks of breast cancer. The status of angiogenesis is important in therapy choice. Spider telangiectasias (telangiectasias) may reflect an increased ability to form vessels. Our first aim was to identify patient and tumor characteristics associated with the occurrence of telangiectasias at the time of breast cancer diagnosis. The second aim was to study the overall survival in relation to the occurrence of telangiectasias at the time of breast cancer diagnosis. A standardized questionnaire was used to interview 1682 consecutive breast cancer patients about risk factors between 1980 and 2009. Occurrence of telangiectasias at the time of breast cancer diagnosis on the upper thorax, head, and/or neck was recorded by one physician. In the cohort, 93 women (5.5%) had telangiectasias. Occurrence of telangiectasias was positively associated with weight, odds ratio (OR) 1.02 (95% confidence interval (CI) 1.00–1.05) per kg, ever-use of oral contraceptives OR 2.67(CI 1.55–4.63) and hormone replacement therapy OR 2.68(CI 1.63–4.39), and negatively associated with parity OR 0.45(CI 0.25–0.79). Telangiectasias were not present in patients with comedo breast cancer. Patients with occurrences of telangiectasias diagnosed before the age of 50 had a statistically non-significant worse overall survival, whereas the patients with occurrences of telangiectasias diagnosed at age 50 or after had a statistically significant better overall survival (P interaction = 0.016). The relationship between the occurrence of telangiectasias and the overall survival in the older patient-group was independent of ever-use of HRT. Hormonal risk factors for breast cancer were associated with the occurrence of spider telangiectasias. The occurrence of telangiectasias may reflect the angiogenic status of the tumor. We hypothesize that telangiectasias could be used as selection criteria for anti-angiogenic therapy in younger breast cancer patients. Therefore, patients with comedo breast cancers maybe a group that may benefit less from anti-angiogenic therapy.     

Margins in breast cancer: How much is enough?

The appropriate negative margin width for women undergoing breast‐conserving surgery for both ductal carcinoma in situ (DCIS) and invasive carcinoma is controversial. This review examines the available data on the margin status for invasive breast cancer and DCIS, and highlights the similarities and differences in tumor biology and standard treatments that affect the local recurrence (LR) risk and, therefore, the optimal surgical margin. Consensus guidelines support a negative margin, defined as no ink on tumor, for invasive carcinoma treated with breast‐conserving therapy. Because of differences in the growth pattern and utilization of systemic therapy, a margin of 2 mm has been found to minimize the LR risk for women with DCIS undergoing lumpectomy and radiation therapy (RT). Wider negative margins do not improve local control for DCIS or invasive carcinoma when they are treated with lumpectomy and RT. Re‐excision for negative margins should be individualized, and the routine practice of performing additional surgery to obtain a wider negative margin is not supported by the literature. Cancer 2018;124:1335‐41 . © 2018 American Cancer Society.     

Incidence and risk factors associated with bilateral breast cancer in area with early age diagnosis but low incidence of primary breast cancer: analysis of 10-year longitudinal cohort in Taiwan

Summary This study aims to examine the incidence and risk factors of bilateral breast cancer in area with low incidence rate. A total of 120 and 1902 women with bilateral and unilateral breast cancers were enrolled; various factors, including those concerning their medical history and life style, were extracted. Using Kaplan–Meier method, we calculate the cumulative incidence of contralateral breast cancer. The results show as follows. The cumulative incidences of contralateral breast cancer at 1, 3, 5 years after diagnosis of first breast cancer were 1.15, 1.94, and 2.97%, respectively. The statistically significant risk factors included menopause (Hazard Ratio (HR) =1.56, (1.00–2.42)), invasive lobular carcinoma (HR=2.98, (1.35–6.56)), receiving chemotherapy (HR=2.21, (1.43–3.42)) and/or radiotherapy (HR=3.32, (2.19–5.05) and a protective factor was tamoxifen therapy (HR=0.5 (0.34–0.74). Size of the second occurred tumour (2.97 cm) tended to be smaller than the first one (3.58 cm) with borderline statistical significance (p=0.0731). Comparing to the existing data on Western countries, we find a higher risk for developing contralateral breast cancer in Taiwan where a low incidence of first breast cancer rate with early age diagnosis is noted. It suggests that first primary breast tumour with early age of onset and lobular carcinoma are found more likely to develop bilateral breast cancers.Tony Hsiu-Hsi Chen and King-Jen Chang equally contributed to this article.     

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall

Introduction

The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non–small cell lung cancer (NSCLC).

Genetic Polymorphisms of eNOS, Hormone Receptor Status, and Survival of Breast Cancer

The endothelial cell-specific form of nitric oxide synthase (eNOS) may play an important role in tumor progression via angiogenesis or apoptosis. We studied eNOS −786T > C and 894G > T (Glu298Asp), two functionally significant SNPs, in relation to hazard of breast cancer recurrence or death in 873 women with incident, non-metastatic breast cancer, recruited from two teaching hospitals in Seoul, Korea, 1995–2002. Hazards were estimated by Cox proportional hazard models, in relation to genotype, adjusting for hormone receptor status, lymph node involvement, and tumor size. Women carriers of the eNOS −786C allele had significantly increased hazards of breast cancer recurrence or death, compared with women having the TT genotype (HR = 2.1, 95% CI = 1.03–4.33); risks increased up to 3-fold in ER positive cases (HR = 3.2, 95% CI = 0.95–10.50). The hazard was also increased in eNOS 894T carriers, however, it did not reach statistical significance (HR = 1.8, 95% CI = 0.85–3.93). The combined genotypes containing −786C or 894T was associated with a 2.5-fold risk, compared to the TT–GG genotypes, the most dominant genotype combination (95% CI = 1.29–4.68), with the greatest risks in ER positive cases (HR = 4.9, 95% CI = 1.31–18.36). These results indicate that the eNOS −786C polymorphism, and possibly the 894T polymorphism, are associated with breast cancer recurrence and death, particularly in women with ER positive tumors.     

Outcomes and factors impacting local recurrence of ductal carcinoma in situ

BACKGROUND: The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR). METHODS: Between 1985-1992, 88 consecutive diagnoses of DCIS were identified in 85 patients. Seventy-four percent were detected mammographically. The most common histologic subtypes were comedo (54%) and cribriform (23%). Tumor sizes were < 2.5 cm (49%), > 2.5-5 cm (26%), > 5 cm (23%), and unknown (2%). Final resection margins were tumor free (75%), close/positive (23%), and unknown (2%). Treatment methods included mastectomy (30%), localized surgery and radiation therapy (LSR) (43%), or wide localized surgery alone (LS) (27%). Radiation therapy (RT) was comprised of 50 grays to the breast, and 53% of treated patients received local "boost" irradiation. RESULTS: The median follow up was 8.3 years. The overall recurrence rate was 13. 6%, whereas the median time to LR was 27.8 months. Recurrence rates according to treatment modality were: LS: 25%; LSR: 13%; and mastectomy: 4%. However, if surgical margins were tumor free, LSR had a LR rate of 3.4%. After RT, no LR occurred prior to 15 months, and 4 of 5 tumors were noninvasive. Nine patients treated by excision alone conformed to the criteria of Lagios et al. criteria and LR occurred in three of nine tumors. Of the factors analyzed, margin status was found to be the best predictor for LR (P = 0.05). CONCLUSIONS: If surgical margins are tumor free, the LSR regimen is equivalent to mastectomy for local tumor control. Annual mammograms may be adequate for the follow-up of patients with irradiated breasts, but biannual studies still are recommended for patients treated with excision alone.     

THE USEFULNESS OF ~(99)Tc-PMT DELAYED HEPATOBILIARY IMAGING IN THE DIAGNOSIS OF SMALL HEPATOCELLULAR CARCINOMA

This investigation was aimed to assess the usefulness of delayed hepalobillary Imaging in the diagnosis of small hepatocellular carcinoma (HCC). Sixty-two patients with this hepatic cancer were Included in the study. 56 males and 6 females, with a mean age of 50. 6 yr. (32 - 72 years old). All patients were performed by surgery, verified histologically, and these tumors were smaller than 5 cm. Liver scans were performed 5 minutes, 2 hours and 5 hours after the administration of radlopharmaceutices. In 31 of the 62 patients (50%), the tumor exhibited equal radioactivity uptake or greater radioactivity uptake than the surrounding liver in delayed imaging. And the sensitivity was 33. 3% (2/6), 41.2% (7/17), 60.0% (9/15) and 54.2% (13/24) In the tumor size was ≤2 cm, 2-3cm, 3-4 cm and 4 - 5 cm, respectively. The smallest mass to be detected was only 1. 2 cm. The uptake of radiopharmaceutic was nonsignificantly related to serum AFP level and hepatic cirrhosis (P>0. 05). These results show that 99-Tc-PMT del