T1-2N0M0 Breast Cancer Research Articles

High expression of cyclin D1 is associated to high proliferation rate and increased risk of mortality in women with ER-positive but not in ER-negative breast cancers

PurposeCyclin D1 has a central role in cell cycle control and is an important component of estrogen regulation of cell cycle progression. We have previously shown that high cyclin D expression is related to aggressive features of ER-positive but not ER-negative breast cancer. The aims of the present study were to validate this differential ER-related effect and furthermore explore the relationship between cyclin D overexpression and CCND1 gene amplification status in a node-negative breast cancer case–control study.MethodsImmunohistochemical nuclear expression of cyclin D1 (n = 364) and amplification of the gene CCND1 by fluorescent in situ hybridization (n = 255) was performed on tissue microarray sections from patients with T1-2N0M0 breast cancer. Patients given adjuvant chemotherapy were excluded. The primary event was defined as breast cancer death. Breast cancer-specific survival was analyzed in univariate and multivariable models using conditional logistic regression.ResultsExpression of cyclin D1 above the median (61.7%) in ER breast cancer was associated with an increased risk for breast cancer death (OR 3.2 95% CI 1.5–6.8) also when adjusted for tumor size and grade (OR 3.1). No significant prognostic impact of cyclin D1 expression was found among ER-negative cases. Cyclin D1 overexpression was significantly associated to high expression of the proliferation markers cyclins A (ρ 0.19, p = 0.006) and B (ρ 0.18, p = 0.003) in ER-positive tumors, but not in ER-negative cases. There was a significant association between CCND1 amplification and cyclin D1 expression (p = 0.003), but CCND1 amplification was not statistically significantly prognostic (HR 1.4, 95% CI 0.4–4.4).ConclusionWe confirmed our previous observation that high cyclin D1 expression is associated to high proliferation and a threefold higher risk of death from breast cancer in ER-positive breast cancer.

Abstract P2-01-27: Sentinel lymph node biopsy by contrast-enhanced ultrasonography with sonazoid in patients with breast cancer - Prospective multicenter study

Abstract Background: The aim of this prospective study is to evaluate feasibility of the periareolar injection of contrast agent (Sonazoid (SNZ)) followed by ultrasonography (US) for identification of sentinel lymph node (SLN) in breast cancer patients with clinically negative node. Patients and Methods: Patients with T1-2N0M0 breast cancer were recruited in this study. They received the periareolar injection of SNZ followed by US to identify contrast-enhanced SLN. Fine needle aspiration biopsy (FNAB) was done for each CE-SLN. Then, they underwent SLN biopsy with the conventional method, blue dye and/or radiotracer (B/R). Results: In almost all cases, contrast-enhanced lymphatic vessels were clearly visualized US soon after the periareolar injection of SNZ, and SLN, into which lymphatic flow was draining, was easily identified. The identification rate of SLN was 98% (98/100) by SNZ and 100% (100/100) by B/R. The number of SLNs identified by SNZ (mean per patient, 1.52) was significantly (P < 0.001) lower than that of those by B/R (2.22). Twenty-five patients had at least one metastasis in the SLNs identified by SNZ and/or B/R. In these patients, SLNs (n=39) identified by both SNZ and B/R showed a significantly (P < 0.0001) higher positivity (74.4%) for metastases than those (n=19) identified by B/R alone (21.1%). Conclusion: Identification of SLN by periareolar injection of SNZ followed by US is a technically easy method and the identification rate of SLN was as high as 98%, being comparable to the conventional B/R. SLNs detected by SNZ seem to represent the true SLNs which first receive lymphatic flow from the tumor among the SLNs detected by B/R. Citation Format: Shimazu K, Ito T, Uji K, Miyake T, Motomura K, Noguchi S. Sentinel lymph node biopsy by contrast-enhanced ultrasonography with sonazoid in patients with breast cancer - Prospective multicenter study [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-01-27.

AUTOMATED ANALYSIS OF CELL DENSITY IN BREAST CANCER AS AN ADDITIONAL METHOD OF INCREASING OBJECTIVITY AND ACCURACY OF BREAST CANCER PROGNOSIS

Introduction . In the last ten years, it became obvious that on the molecular level breast cancer is a group of heterogenous tumors. The current objective of routine clinical practice of treatment prescription includes accurate disease prognosis for every individual patient and conviction that the risk of breast cancer recurrence after adjuvant hormone therapy without adjuvant chemotherapy doesn’t increase. The study objective is to evaluate how clinical use of risk associated with cell density can in practice improve prognosis of recurrence risk in patients with breast cancer after standard clinical and pathomorphological examinations. Materials and methods . The article analyzes therapy results using data from the cumulative cancer registry of breast cancer diagnosis and treatment of the N.N. Petrov National Medical Research Oncology Center in 2000–2009. The database includes information on diagnosis, treatment, and survival of 5106 patients with breast cancer. Archived material (from 2000 to 2009) from paraffin blocks of the “targeted group” for methods of molecular and genetic profiling was poured into recipient blocks, stained with corresponding antibodies such as widely used ER, PR, HER2/neu, Ki-67 markers as well as poorly studied markers: cell density, р53, CK5/6, CK14, CD4/CD8, p63, EGFR, FOXP3, AR, FOX1. Results . The study of 1118 patients with stage T1–2N0M0 breast cancer has shown that analysis of risk associated with cell density allows to predict disease outcome. Correlation between the marker and the grade of histological malignancy is more rare than for Ki-67 determined in this patient group. As a result, determination of cell density is an additional method to increase objectivity and accuracy of breast cancer prognosis. Conclusions . Automated cell density analysis for breast cancer is almost fully operator-independent which increases accuracy and objectivity of the results. Cell density in breast cancer lower than 3000 cells/mm 2 is a favorable prognostic factor.

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial, SweBCG 91 RT

BackgroundBreast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients. Patients and methodsA total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program. ResultsAfter 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P<0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P=0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P=0.68, nor was breast cancer–specific mortality significantly higher. ConclusionsRT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.

DVH comparison beween forward IMRT, inverse IMRT & RapidArc® for patients with left sided breast cancer after lumpectomy

Introduction When patients with left sided breast cancer are treated with adjuvant radiotherapy after lumpectomy, a significant volume of the heart and the left descending coronary artery (LDCA) receive enough radiation to result in serious late cardiac morbidity. This study dosimetrically compares the following three delivery techniques: forward intensity-modulated therapy (F-IMRT), inverse intensity-modulated therapy (I-IMRT), and volumetric-modulated arc therapy (RapidArc® in terms avoiding the heart and the LDCA. Other DVH parameters were also studied. Purpose The primary aim of this study is a feasibility check for the use of RapidArc®technique for breast radiotherapy to our department, as well as the identification of the potential advantages of RapidArc®into clinical routine. A secondary aim is a non inferiority check of RapidArc® versus conventional IMRT. Materials and methods Twenty patients with T1-2N0M0 breast cancer of the left breast who were treated with I-IMRT after lumpectomy were re-planned with F-IMRT and RapidArc® using Eclipse™ Treatment Planning System form Varian medical systems. Comparative endpoints were consider to be the doses to the surrounding structures, Conformity Index (CI), Homogeneity Index (HI), number of monitor units (MUs) and treatment delivery time. Statistical program SPSS was used in order to investigate the null hypothesis of this study: “No difference exists in distribution of various dosimetric scores between the three techniques”. Results RapidArc® significantly reduced the dose received from the 50% volume of the LDCA compared with I-IMRT and F-IMRT. RapidArc® and I-IMRT had better CI compared with F-IMRT but F-IMRT achieved better HI compared with I-IMRT and RapidArc®. RapidArc® reduced the number of MUs by 47% and the treatment time by 70% compared with I-IMRT. Conclusion RapidArc® achived better sparing of LDCA, with fewer MUs and shorter delivery time than F-IMRT and I-IMRT. Conformity significantly higher with RapidArc® and I-IMRT compared to F-IMRT. Disclosure No conflict of interest, financial or other, exists.

Ten-year survival results of ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node (Alliance).

1007Background: The early results of ACOSOG Z0011 showed that selected sentinel node (SN)-positive patients (pts) treated with sentinel node biopsy (SNB), whole breast irradiation, and adjuvant systemic therapy experienced overall survival (OS) and disease-free survival (DFS) not inferior to those treated with axillary lymph node dissection (ALND). There were concerns that the follow-up was inadequate to assure non-inferiority. The 10-year survival results of Z0011 are reported here. Methods: Clinically node-negative pts with 1 or 2 SNs with H&E-detected metastases were randomized to ALND or no further axillary specific treatment. All pts were to receive whole breast irradiation and systemic therapy. OS and DFS were evaluated. Results: 446 pts were randomized to SNB alone and 445 to SNB + ALND. Pts in both arms were similar with respect to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and stage. Pts randomized to SNB alone had a median of two lym...

Sentinel Lymph Node Detection in Breast Cancer – First Experience/ Детекција На Сентинелни Лимфни Јазли Кај Карцином На Дојка – Први Искуства

Breast cancer accouns for 22.9% of all cancers in women and 13.7% of cancer deaths. Positive axillary lymphnodes (ALN) predict the development of distant metastases. The status of the sentinel lymphnode (SLN) is crutial for the treatment selection. To determine the benefits of SLN detection in patients with breast cancer. 38 female patients (pts), age 44 ± 12 years, with T1-2 N0 M0 breast cancer, without enlarged ALN on ultrasound (US), were included. SLN detection was performed using gamma camera and gamma detection probe after periareolar subcutaneous and/or peritumoral injection of (99m-Technetium-SENTISCINT). Blue dye was administered 20 min before the operation. SLN was extirpated and ex tempore histopathology was performed. Ex tempore SLN evaluation was negative and the lymphatic pathways preserved in 28/38 (74%) pts. In 10/38 (26%) pts SLN was positive, followed by radical surgery. In 3/28 ex tempore negative patients, histopathological analysis showed metastatic involvement (false negative). In 3/10 ex tempore positive patients micro metastases 0,2-2 mm were detected. 12 pts had 2 SLN, 8/12 (66%) had negative and 4/12 (34%) had positive SLN. 3 pts had a rare double drainage to axilla and a. mammaria int. Our results confirm that SLN detection technique is non-invasive, safe and reliable and should be incorporated into the guidelines for breast cancer pts (T1-2 N0 M0). The most reliable option for colloid application is the combined technique of periareolar and peritumoral injection. Patients with drainage to a. mammaria interna should be selected for adjuvant protocols.

Abstract P2-01-09: Application of the Z0011 criteria on Dutch breast cancer patients

Abstract Background The American College of Surgeons Oncology Group reported a randomized controlled trial (Z0011-trial) among women with T1-2N0M0 breast cancer treated with breast conserving therapy. It showed that axillary lymph node dissection may be redundant in selected sentinel node positive patients. Though, it raises questions as to the general applicability of these results. Therefore, this study aims to examine the practice changing effect and the clinical relevance of the criteria described in the Z0011 trial, when applied to a Dutch population of patients diagnosed with invasive breast cancer. Methods This is a multicenter study including patients with T1-2N0-1M0 invasive breast cancer treated in either of the 10 different hospitals affiliated with the Dutch National Cancer Registry region South in the period between January 2007 and December 2012. All patients underwent a clinical examination, a mammography and sonographic examination of the breast and the ipsilateral axilla. Chi-square analyses or a Fisher’s exact test were used to assess differences in patient and tumor characteristics the Z0011 population and the Dutch cohort. A p-value of ≤0.05 was considered statistically significant. Results A total of 11,031 patients had invasive breast cancer, of whom 5368 patients were treated with breast conserving therapy. In 6.8% axillary status was determined by the ultrasound guided lymph node biopsy and in 93.1% axillary metastases were found trough the sentinel node procedure after a negative or inconclusive ultrasound. When applying the Z0011 criteria to our study population of node positive patients, 5.7% of all breast cancer patients, equalling 11.8% of patients receiving breast conserving therapy, met the Z0011 criteria. Conclusion These results suggest that when applying the Z0011 criteria to all node positive patients, including patients with a positive sentinel node and patients with a positive ultrasound guided lymph node biopsy, only in 5.7% of all invasive breast cancer patients could be spared an ALND and its morbidity. This is a small practice changing effect. Nevertheless, it is worthwhile to consider implementing the findings of Z0011 trial in daily clinical practice. Citation Format: Nicole C Verheuvel, Vivianne CG Tjan-Heijnen, Adri C Voogd, Rudi MH Roumen. Application of the Z0011 criteria on Dutch breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-01-09.

Tumor location is a prognostic factor for survival of Chinese women with T1-2N0M0 breast cancer

ObjectiveThe purpose of this study was to investigate the effects of primary tumor location on the survival of Chinese women with T1-2N0M0 breast cancer. MethodsThe clinical data of 1044 patients with stage T1-2N0M0 breast cancer who were treated from 1999 to 2007 were retrospectively analyzed. Patients were divided according to the primary tumor location: upper-outer quadrant (UOQ), upper-inner quadrant (UIQ), lower-outer quadrant (LOQ), lower-inner quadrant (LIQ), and nipple and central breast (central). The effect of primary tumor location on recurrence-free survival (RFS) and overall survival (OS) were determined. ResultsThe median age at diagnosis was 47 years. The tumor was located in the UOQ in 524 patients (50.2%), the LOQ in 124 (11.9%), the UIQ in 229 (21.9%), the LIQ in 59 (5.7%), and centrally in 108 patients (10.3%). The 5- and 10-year RFS and OS of the LIQ group were significantly poorer than that of patients in the other groups (RFS: 72.1% vs. 82.2–86.7%, P = 0.041; OS: 73.6% vs. 85.3–89.1%, P = 0.024). Multivariate Cox analysis showed that primary tumor location in the LIQ was an independent prognostic factor for RFS (hazard ratio [HR] = 2.977; 95% confidence interval [CI] 1.219–7.273; P = 0.017) and OS (HR = 2.949; 95% CI 1.207–7.208; P = 0.018). ConclusionPrimary tumor location is an important prognostic factor for survival of Chinese women with T1-2N0M0 breast cancer.

Abstract P3-02-02: Cyclin D1 overexpression increases the risk for breast cancer death 4-fold in hormone receptor positive and node negative breast cancer

Abstract Background: Cyclin D1 has a central role in cell cycle control, but also directly affects the estrogen receptor. It has been shown that cyclin D can activate the estrogen receptor in a ligand-independent way and studies are implying that cyclin D overexpression may be linked to tamoxifen resistance. We wanted to explore the prognostic value of cyclin D overexpression in node negative breast cancer. Patients and methods: We examined the expression of cyclin D1 using immunohistochemistry on tissue micro array (TMA) sections from a case control study (1:1) consisting of 380 patients with T1-2N0M0 breast cancer. Adjuvant radiotherapy and endocrine treatment was allowed, but not chemotherapy. Event was defined as breast cancer death. Breast cancer specific survival was analyzed in univariate and multivariate models using conditional logistic regression. Results: Cyclin D1 was inversely correlated to Elston grade (rho = 0.2; p = 0.000); moderately correlated to PgR status (rho = 0.3, p = 0.000) and strongly correlated to ER status (rho = 0.4, p = 0.000). Cyclin D1 overexpression did not increase the risk for breast cancer death analyzing the whole patient population. However, subgroup analyses of hormone receptor positive patients showed an increased risk for breast cancer death (OR 4.2; 95% CI 1.4-12.6) and (OR 3.9; 95% CI 1.3-12) when adjusted for tumor size and age at diagnosis.Conclusion: Cyclin D1 is an independant prognostic factor of outcome in hormone receptor positive and node negative breast cancer with overexpression increasing the risk for breast cancer death 4-fold. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-02-02.

A comparison of quality of life and satisfaction of women with early-stage breast cancer treated with breast conserving therapy vs. mastectomy in southern China

The purpose of this study was to compare the quality of life (QoL) and overall satisfaction with treatment of women with stage T1-2N0M0 breast cancer treated with breast conserving therapy (BCT) or mastectomy (MAS) in southern China. Functional assessment of cancer therapy-breast, traditional Chinese version 4 (FACT-B), was administered to 180 patients with stage T1-2N0M0 breast cancer (82 BCT and 98 MAS) treated between July 2000 and July 2008. The two groups differed in tumor pathology and how axillary lymph nodes were treated (sentinel node biopsy vs. dissection), while other disease and socioeconomic characteristics were similar. The median follow-up after completion of radiotherapy was 60 months in the BCT group, and 65 months in the MAS group. The scores of the physical, functional, and emotional domains and breast-specific concerns of FACT-B were not significantly different between the groups. The social domain score of the BCT group was significantly greater than those of the MAS group. Patients who underwent BCT did not report better QoL than those who received MAS, but BCT patients experienced easier social adjustment.

The role of Ki-67 proliferation index vis-à-vis Oncotype DX.

e11055 Background: Most newly diagnosed patients with invasive breast cancer have node negative disease. A key question in management of these patients is the risk/benefit ratio of adjuvant chemotherapy. Several microarray tests have been developed and are currently used to help identifying the patients who will benefit from adjuvant chemotherapy. Ki 67 proliferation index is less expensive and has been used as a prognostic and predictive factor in node positive breast cancer and neoadjuvant setting. Methods: Forty five cases of T1-2 N0 M0 (ER positive, HER2/neu negative) breast cancer were reviewed. Oncotype Dx results were available for all patients. Tumor specimens were stained for Ki 67. Results: The median of Ki 67 index was 17 (range 2-90). The median Oncotype recurrence score was 17 (range 7-60). There was a strong linear correlation between Ki67 index and Oncotype recurrence score (correlation coefficient= 0.74, P value= 0.000). This correlation was stronger in tumors with Ki 67 proliferation inde...

Abstract P4-10-03: Long-Term Follow-Up of SweBCG 91RT, a Randomized Trial of Breast Conservation Surgery with and without Radiotherapy from the Swedish Breast Cancer Group

Abstract Background: Postoperative radiotherapy remains the golden standard after breast conservation surgery. However, national breast screening programmes and increased public awareness of breast cancer have resulted in earlier detection of small tumours with favourable prognosis. The Swedish SweBCG 91RT multicentre study of breast conservation with and without radiotherapy was initiated in 1991. Five year results have been published.(Malmström P et al. Eur J Cancer 39: 1690, 2003). A gene expression signature for radioresistance has also been defined from this patient material. (Niméus-Malmström E et al. Breast Cancer Res 2008, 10:R3(doi10:1186/brc1997). Increasing knowledge of genetically defined subgroups of breast cancer is likely to have an impact on breast conservation treatment. We now present outcome after 15 years of follow-up. Patients and methods: After a standardised radical sector resection 1187 patients with T1-2N0M0 breast cancer were randomised to postoperative radiotherapy or no further treatment. 1178 patients fulfilled the inclusion criteria. The two treatment groups were well balanced with respect to prognostic factors. Median tumour size was 12 mm, and 65 % of cases were detected by mammography screening. Radiotherapy with tangential MV photons, 48-54 Gy in 24-27 fractions, was administered to the remaining breast parenchyma. CT-based 3-D treatment planning was used. Adjuvant systemic therapy was prescribed according to regional treatment programmes. Nine percent received adjuvant systemic therapy. Patients were followed annually with bilateral mammography for 10 years and thereafter referred to the national Swedish breast screening programme. Results: With a median follow-up of 15 years, the addition of postoperative radiotherapy did not affect overall survival, 70.8 % with RT vs 68.2 % without RT, p=0.79. This result is based on follow-up for survival until April 2010 for all patients. However, recurrence-free survival, RFS, was significantly improved by radiotherapy, 62,6 % vs 53.7 % after 15 years, P&amp;lt;0.001. The cumulative incidence of local recurrences as first event was significantly lower in the irradiated group 11.8 % after 15 years compared to 24.3 % in the control group, P&amp;lt;0.0001. Results for RFS and local recurrences are based on prolonged follow-up of 85 % of the cases and to 1999 for the remaining. Data with more complete follow-up will be presented at the meeting as will data on treatment efficacy in predefined subgroups. Conclusions: Postoperative breast radiotherapy is indicated for the majority of patients operated with breast conservation surgery. Analysis of treatment efficacy in subgroups of patients may identify groups for which radiotherapy can be omitted in the future. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-10-03.

ACOSOG Z0011: A randomized trial of axillary node dissection in women with clinical T1-2 N0 M0 breast cancer who have a positive sentinel node.

CRA506 Background: Sentinel node biopsy (SNB) eliminates the need for axillary dissection (ALND) in patients whose sentinel node (SN) is tumor-free. However, completion ALND remains the gold standard for patients with a tumor-involved sentinel node. ALND achieves regional control, but its effect on survival remains controversial. The main objective of ACOSOG Z0011 was to compare outcomes of patients with hematoxylin and eosin (H&amp;E) detected metastasis in SN managed with or without ALND and no axillary irradiation. Methods: Clinically node-negative patients who underwent SN biopsy and had 1 or 2 SN with metastases detected by H&amp;E were randomized to ALND or no further axillary specific treatment. All patients were treated with lumpectomy and opposing tangential field irradiation. Adjuvant systemic therapy was at the discretion of their physicians. Overall survival (OS), disease-free survival (DFS), and locoregional control were evaluated. Results: 446 patients were randomized to SNB alone and 445 to SNB plus ALND. Patients treated with SNB alone were similar to those treated with SNB + ALND with respect to age, tumor size, Bloom-Richardson score, estrogen receptor status, adjuvant systemic therapy, tumor type, and T stage. Patients randomized to SNB alone had a median of two lymph nodes removed whereas patients randomized to ALND had a median of 17 lymph nodes removed. 17.6% of ALND patients had 3 or more involved nodes compared to 5.0% of SNB patients (p &lt; 0.001). Median follow-up is 6.2 years. 5-year in breast recurrence after ALND was 3.7% compared to 2.1% for SNB (p = 0.16) while 5-year nodal recurrence was 0.6% compared to 1.3% (p = 0.44) respectively. The five-year OS for patients undergoing SNB + ALND is 91.9% compared to 92.5% for SNB alone (p = 0.24), and DFS is 82.2% compared to 83.8% respectively (p = 0.13). Conclusions: Despite the widely held belief that ALND improves survival, no significant difference was recognized by this study of SN node-positive women. Although the study closed early because of low accrual/event rate, it is the largest phase III study of ALND for node-positive women, and it demonstrates no trend toward clinical benefit of ALND for patients with limited nodal disease. [Table: see text]

The effect of radiocolloid preference on major parameters in sentinel lymph node biopsy practice in breast cancer

The possible effects of radiocolloid preference on sentinel lymph node biopsy (SLNB) were investigated. A total of 200 patients with T1-2N0M0 breast cancer were evaluated. The first 100 patients underwent SLNB using (99m)Tc tin colloid (TC) and the next 100 using (99m)Tc nanocolloid (NC). Radiocolloid was injected intradermally at four quadrants of the periareolar region the day before surgery. All patients underwent lymphoscintigraphy 1 h after injection. All nodes having fourfold activity of the background were harvested using gamma probe. Sentinel lymph node (SLN) identification rate by gamma probe was 98% in each group. The number of SLNs identified by lymphoscintigraphy, gamma probe and pathological evaluation was 1.39 ± 0.7, 1.70 ± 1.0 and 2.23 ± 1.70 in the TC and 2.03 ± 0.94, 2.60 ± 1.36 and 3.05 ± 1.90 in the NC group, respectively (P<.05). Metastatic SLN was found in 24 (24.4%) of 98 patients in the TC group and 41 (41.8%) of 98 patients in the NC group (P=.04). None of the patients showed dispersion to internal mammarian lymph nodes. Lymphatic vessel visualization was observed in eight (8.1%) of 98 TC patients and in 47 (47.9%) of 98 NC patients (P=.000). SLNs were the only metastatic node(s) in 54.1% of TC and 73.1% of NC patients. The periareolar intradermal injection technique gives a high detection rate in the localization of SLNs independently from the choice of the tracer. Mean SLN numbers and lymphatic vessel visualization frequency were significantly higher using a smaller albumin Tc-99m nanocolloid as compared to a stannous fluoride Tc-99m tin colloid. The results of our study support the idea that the influence of increased number of SLNs on positive SLN frequency is critical.

Plasma Retinol and Prognosis of Postmenopausal Breast Cancer Patients

The role of retinol (vitamin A) in breast cancer prognosis has never been investigated in postmenopausal women. We prospectively assessed the long-term prognostic role of retinol plasma levels in a cohort of postmenopausal breast cancer patients. We investigated 208 women self-reported as postmenopausal operated on for T(1-2)N(0)M(0) breast cancer who participated in a chemoprevention trial as controls and never received chemotherapy or hormone therapy. Plasma samples were collected 3 months (median) after surgery and assayed within 3 weeks for retinol. Minimum and median potential follow-up were 12 and 15 years, respectively. The main analyses were on all women and on a subgroup ages >or=55 years, assumed too old to be in perimenopause. The main end point was breast cancer death. Breast cancer survival was estimated by the Kaplan-Meier method. The hazard ratios of breast cancer death by retinol level were estimated by Cox models stratified for age, where relevant, and recruitment period, and adjusted for tumor size and histology. At 12 years, patients with low retinol (<2.08 micromol/L, median of distribution) had lower breast cancer survival than those with high retinol (log-rank P = 0.052); the difference was significant for women >or=55 years (log-rank P = 0.006). The adjusted hazard ratios for low versus high retinol were 2.11 (95% confidence interval, 1.08-4.14) for all women and 3.58 (95% confidence interval, 1.50-8.57) for those >or=55 years. Low plasma retinol strongly predicts poorer prognosis in postmenopausal breast cancer patients. Retinol levels should be determined as part of the prognostic workup.

DNA flow cytometry does not predict 5- or 10-year recurrence rates for T1-2 node-negative breast cancer.

A small proportion of T1 or T2 node-negative breast cancer tumors will recur in patients by 5 years, and more by 10 years. Results of recent studies have suggested improvement in overall survival with administration of adjuvant chemotherapy to all patients. More sensitive and specific methods are needed to identify patients at highest risk for recurrence who might benefit most from adjuvant therapy, saving others from unnecessary treatment. Some investigators have suggested DNA flow cytometry as a method to discriminate patients at greatest risk for recurrence. DNA flow cytometry has predictive value for breast cancer recurrence in node-negative patients. The cancer registry of a medium-sized university-affiliated hospital was used to identify patients with T1-2 N0 M0 breast cancer treated with a uniform surgical approach and no adjuvant therapy who had completed at least 5 years of follow-up or had recurrence. Flow cytometric analysis was performed on paraffin-embedded specimens. Of 115 patients, 92 (80%) had disease-free survival without recurrence and 23 (20%) had recurrence. Comparison of diploid and nondiploid tumors for likelihood of recurrence revealed no association (P = .79). Furthermore, the DNA index and S-phase fraction were not significantly different between recurrent and nonrecurrent groups. The likelihood of recurrence of small node-negative breast cancers after mastectomy cannot be accurately predicted on the basis of DNA flow cytometric analysis. Traditional methods for determining risks-such as nuclear and histological grade, lymph node status, and tumor size-seem to be more useful. Sentinel lymph node biopsy techniques may increase the detection of micrometastases.