Comparing an AI test to a 21-gene assay for premenopausal node-positive HR+/HER2-breast cancer

ObjectiveOur study aims to clarify the role of estradiol and leptin in breast cancer risk and prognostic assessment in postmenopausal Chinese women.DesignThe serum circulating estradiol and leptin level was detected by ELISA. Then the correlation between estradiol, leptin level, and clinical characteristics was analyzed using Fisher’s exact test. Next, the Kaplan-Meier model was used to analyze the association between estradiol, leptin, and prognosis of postmenopausal breast cancer patients in our cohort and the TCGA dataset.SettingThe study was conducted at the National Cancer Center, Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College.PatientsA total of 182 postmenopausal breast cancer patients and 111 healthy subjects from January 2010 to August 2010 were included in the analysis. Another 702 cases with breast cancer were retrieved from The Cancer Genome Atlas (TCGA) database for subsequent analysis.Main Outcome MeasureSerum circulating estradiol and leptin level.ResultsThe level of estradiol was significantly higher (P<0.001) but the level of leptin had no significant difference (P = 0.764) in postmenopausal breast cancer patients compared with healthy subjects. The level of estradiol and leptin was not significantly different between estrogen receptor (ER) positive and ER-negative groups (P>0.05). Estradiol was significantly correlated with tumor T stage (P = 0.002) and leptin was significantly associated with perineural invasion (P = 0.014). In addition, the disease-free survival of patients with a high level of estradiol was significantly shorter (P = 0.025) but leptin tended to be a protective factor for overall survival in TCGA analysis (P = 0.038).ConclusionCirculating estradiol and leptin played important roles in the risk of postmenopausal breast cancer even in low-estrogen nations with an independent expression of ER status. High circulating estradiol was a poor prognostic factor and leptin may be a protection signal in Chinese postmenopausal patients with breast cancer.

Data on 130 women with invasive breast cancer, seen at our institution between April 1981 and November 1990, were retrospectively reviewed to assess the influence of age and menstrual status on the pattern and prognosis of their disease. Patients were mostly young (median age 40 years) and in 21 patients (16%) the diagnosis was established at the age of 30 years or younger. Eighty-six patients (66%) were under 50 and 82 patients (63%) were pre-menopausal. Pre-menopausal patients were more numerous than expected in stage III and less numerous in stage II. On the other hand, the differences between observed and expected values for both stage I and stage IV in the 2 menopausal groups were not significant. Compared with post-menopausal patients, pre-menopausal patients with 1-3 or greater than 3 positive lymph nodes were more numerous than expected. Differences between pre-menopausal and post-menopausal patients have persisted after categorizing patients into 2 age-groups with a cut-off point at 50 years. Comparable initial assessment and therapeutic modalities were offered to the 2 menopausal groups. At the time of analysis (January, 1991) all patients had a complete follow-up. Over a median follow-up of 46 months, the overall median survival (+/- SE) was 85.7 (+/- 4.4) months with a survival probability (+/- SE) at 5 years of 62% (+/- 5%). The proportional hazard model of Cox has identified advanced stage (stages III and IV) and involvement of lymph nodes as the only independent adverse predictors of survival with estimated hazard rates of 2.9 and 2.8, respectively. Unadjusted analysis, adjusted analysis and stratified survival functions failed to reveal any survival difference based on age or menstrual status. We conclude that, in a low-risk population and despite apparent baseline differences in demographic and disease characteristics between pre-menopausal and post-menopausal breast cancer patients, neither age nor menopausal status had a significant influence on survival. Our results should guide future cancer-care programs in Saudi Arabia.

More than half of patients with early-stage estrogen receptor-positive (ER+) breast cancer relapse after completing 5 years of adjuvant endocrine therapy, so it is important to determine which patients are candidates for extended endocrine therapy. The clinical treatment score after 5 years (CTS5) is a prognostic tool developed based on postmenopausal ER+ breast cancer to assess the risk of late distant recurrence (LDR) after 5 years of adjuvant endocrine therapy for breast cancer. We aimed to externally validate the prognostic value of CTS5 in premenopausal and postmenopausal patients and combined with Ki-67 to develop a new model to improve the ability of prognosis prediction. We included a total of 516 patients with early-stage ER+ breast cancer who had received 5 years of adjuvant endocrine therapy and were recurrence-free for 5 years after surgery. According to menopausal status, we divided the study population into 2 groups: premenopausal and postmenopausal women. The CTS5 of each patient was calculated using a previously published formula, and the patients were divided into low, intermediate, and high CTS5 risk groups according to their CTS5 values. Based on the results of the univariate analysis ( P <0.01), a multivariate COX proportional hazards regression analysis was conducted to establish a nomogram with significant variables ( P <0.05). The discriminative power and accuracy of the nomograms were assessed using the concordance index (C-index), calibration curve, and area under the time-dependent receiver operating characteristic curve. Discrimination and calibration were evaluated by bootstrapping 1000 times. Finally, we utilized decision curve analysis to assess the performance of our novel predictive model in comparison to the CTS5 scoring system with regard to their respective benefits and advantages. The median follow-up time was 7 years (6 to 9 years). The 516 women were categorized by CTS5 as follows: 246(47.7%) low risk, 179(34.7%) intermediate risk, and 91(17.6%) high risk. Using the CTS5 score as a continuous variable, patients' risk score was significantly positively associated with recurrence risk in both premenopausal and postmenopausal subgroups. For HER2- premenopausal patients and HER2+ postmenopausal patients, the CTS5 score was positively correlated with LDR risk. Patients with a Ki-67≥20% had a higher risk of LDR regardless of menopausal status. Using the CTS5 score as a categorical variable, the high-risk group of HER2- premenopausal patients had a higher risk of LDR. However, the CTS5 model could not distinguish the risk of LDR in different risk groups for HER2+ postmenopausal patients. In the high-risk group, patients with Ki-67≥20% had a higher risk of LDR, regardless of menopausal status. We developed a new nomogram model by combining the CTS5 model with Ki-67 levels. The C-indexes premenopausal and postmenopausal cohorts were 0.731 and 0.713, respectively. The nomogram model was well calibrated, and the time-dependent ROC curves indicated good specificity and sensitivity. Furthermore, decision curve analysis demonstrated that the new model had a wider and practical range of threshold probabilities, resulting in an increased net benefit compared with the CTS5 model. Our study demonstrated that the CTS5 model can effectively predict the risk of LDR in early-stage ER+ breast cancer patients in both premenopausal and postmenopausal patients. Extended endocrine therapy is recommended for patients with Ki-67≥20% in the CTS5 high-risk group, as well as premenopausal patients with HER2-. Compared with CTS5, the new nomogram model has better identification and calibration capabilities, and further research is required to validate its efficacy in large-scale, multicenter, and prospective studies.

Background: Gene profiling technology, which assesses multiple genes, has garnered attention as a research tool for personalized cancer treatment and its use is recommended in several international guidelines. Currently, postoperative adjuvant therapy for ER-positive and HER2-negative breast cancer includes a wide range of options, including anthracyclines and taxanes, CDK4/6 inhibitors, and TS-1, in addition to hormone therapy. 21-gene signature assay categorizes patients into two groups for assessing adjuvant chemotherapy efficacy: RS 0-25 and RS 26 or higher for N1 patients. However, the broad clinical range of RS 0-25 complicates treatment decisions when relying solely on this cutoff. And over-treatment of the good prognosis group cannot be ruled out. Moreover, in premenopausal patients with N1, optimal prognostic tools have not been established. Curebest™ 95GC Breast (95GC) provides a 95-gene signature that stratifies patients into two groups: high-risk (95GC-H) and low-risk (95GC-L), predicting the recurrence risk and is clinically indicated only for ER-positive, HER2-negative, node-negative invasive (ER+/HER2-/N0) invasive breast cancer. This study aims to investigate the applicability of 95GC in N1 cases and also to discuss the correlation between RS of 21-gene signature assay and 95GC determination. Methods: We reviewed our institutional databases to identify patients with ER-positive, HER2-negative, node-positive breast cancer who had 21-gene signature assay data available and who had undergone definitive surgery between April 2005 and May 2018 and adjuvant endocrine therapy without any cytotoxic agents. We included only patients for whom archival FFPE tissue from definitive surgery was available. We excluded patients with pathological node-negative, distant metastatic disease, and male patients. The Fisher exact test was used to compare variables between 95GC groups. A Kaplan-Meier estimate with a log-rank test was used for survival analysis. Results: A total of 58 patients from our institution were initially included in the analysis; one patient was excluded due to indeterminate HER2-ISH results, resulting in a final cohort of 57 patients including premenopausal patients. When the index cutoff value to distinguish between the 95GC-H and 95GC-L groups was set at 50, the 5-year recurrence-free survival (RFS) rate and the lower limit of the 95% confidence interval were significantly higher in the L group. The L group showed a markedly better prognosis compared to the H group (92.8% and 64.8%; p=0.0063). This cutoff value was consistent with the reference value used for N0 patients. We classified 48 patients (84.2%) as 95GC-L; 9 patients (15.8%), as 95GC-H. The median follow-up duration was 87.3 months. There were no statistical differences in age, menopausal status, T stage, nuclear grade, histological grade, or PR status between the 95GC-H and 95GC-L groups. There were 6 patients (10.5%) of recurrence within 5 years after surgery and 2 of which were distant metastases, both in the 95GC-H group. 5-year distant recurrence-free survival (DRFS) was significantly better in the 95GC-L group than in the 95GC-H group (100% and 77.8%; p=0.0164). The sensitivity and specificity of 95GC for predicting recurrence were 44.4% and 89.6%, respectively. Comparable calculations were conducted for the RS0-25 and RS≥26 groups of 21-gene signature assay, revealing sensitivity and specificity values of 11.1% and 100%, respectively. These results indicate that 95GC demonstrates a higher sensitivity equivalent index compared to 21-gene signature assay. Conclusions: 95GC can predict recurrence risk in patients with ER+, HER2-, N1 breast cancer. It also suggested that it may be able to predict the risk of recurrence better than RS of 21-gene signature assay. Citation Format: Asako Tsuruga, Sachiyo Tada, Hayato Niiro, Kei Hagino, Yusuke Tsukuda, Motonari Daito, Kazuya Kashiwa, Yuka Matsushima, Moeka Tanaka, Reika Yoshida, Seigo Nakamura, Naoki Hayashi, Hiroko Masuda. Investigating the expansion of 95-gene signature (Curebest® 95GC Breast) indication for predicting the risk of recurrence in patients with ER-positive and lymph node-positive breast cancer [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-04-29.

OBJECTIVES:In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations.METHODS:Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated.RESULTS:The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations.CONCLUSIONS:Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER) concentrations in breast cancer tissues were examined in an attempt to establish a possible association between hormones and breast cancer risk and to elucidate the biological features of the disease among Egyptian female patients. Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4 and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-radioreceptor assay. Levels of T and prolactin showed a significant increase in both premenopausal and postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r = -0.26). This study provides evidence of an association between high levels of serum E2 and T and increased risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer development.

As the prognosis of early breast cancer patients improves, the long-term safety of aromatase inhibitors (AIs) is increasingly important. In the present study, we retrospectively investigated the incidences of musculoskeletal disorders (MSDs) and bone fractures in a cohort of Chinese postmenopausal patients with breast cancer. Data of postmenopausal patients with breast cancer were collected. Among which, 70 patients received AIs therapy (median follow-up of 32.5 months), 52 patients received tamoxifen (TAM), and 89 patients received no endocrine therapy (NE). Baseline characteristics, incidence of MSDs and bone fractures were analyzed and compared. When compared with NE group (40.4 %, 36/89), more patients in AIs group developed MSDs (72.9 %, 51/70, adjusted odds ratio (AOR) = 3.30, 95 % confidence interval (CI) = 1.59-6.88, P = 0.001). But no difference was found between TAM group (36.5 %, 19/52, AOR = 0.70, 95 % CI = 0.32-1.52, P = 0.372) and NE group. About 39.7 months after initial AIs therapy, nine patients in AI group developed bone fractures in different sites, and the bone fracture rate was significantly increased (12.9 %, 9/70, adjusted hazard ratio (AHR) = 20.08, 95 % CI = 1.72-234.08, P = 0.017) in comparison with NE group (1.1 %, 1/89). Moreover, the bone fracture rate of TAM group was not different from NE group (1.9 %, 1/52, AHR = 2.64, 95 % CI = 0.14-48.73, P = 0.513). AIs therapy may induce increased rates of MSDs and bone fractures in Chinese population of postmenopausal breast cancer patients, whereas TAM therapy did not help reduce the incidences of MSDs and bone fractures.

Background: Breast cancer is the commonest malignancy among women globally. It is a leading cause of cancer death in less developed countries and the second leading cause of cancer death in developed countries. Diabetes and breast cancer are two conditions that frequently coexist, and menopause may be a metabolic watershed. The purpose of this study is to examine the relationship between glycosylated haemoglobin (HbA1c) and anthropometric measurements in premenopausal and postmenopausal breast cancer patients Methods: 100 patients diagnosed with breast cancer between December 2020 to November 2022 were evaluated and their HbA1c levels were correlated with anthropometric measurements and tumour characteristics Results: In our study mean age of the patients was 47.75 ±11.77 SD years. In patients with normal HbA1c 64% patients were pre-menopausal. In Pre-diabetic HbA1c group 70% were post-menopausal and in diabetic HbA1c group 93% were postmenopausal. Mean waist circumference was 84.56 ± 6.64 SD cms; more in pre-diabetic and diabetic patients; (p value 0.000). Most of the patients (71%) had waist to hip ratio ≥0.85 (p value 0.349). Pre-diabetic and diabetic patients were overweight (p value 0.000). 6 patients were known cases of type II diabetes mellitus and were on insulin/OHAs. T3 tumours were more common in both premenopausal and postmenopausal patients followed by T4 tumours. Stage IIB breast cancer was present in 39% of premenopausal and stage IIIA was seen in 30% of the postmenopausal patients. Grade II disease was more common in both premenopausal and postmenopausal (p value 0.858). Invasive ductal carcinoma-No special type (IDC-NST) was seen in 77% of the patients (p value 0.156). Estrogen Receptor (ER) positivity was seen in 42% of premenopausal and 33% of postmenopausal patients, negative Progesterone Receptor (PR) seen in 86% in premenopausal and 89% in postmenopausal patients and positive Her2 neu receptor was observed in 30% in premenopausal and 56% in postmenopausal patients. Conclusion: Our study demonstrated that a considerable proportion of breast cancer patients were prediabetic. Glycaemic status and HbA1c were clearly associated with measures of visceral obesity in carcinoma of breast patients. Postmenopausal patients had higher levels of HbA1c compared to premenopausal cases. However; clinicopathological and tumour characteristics in our study didn’t demonstrate any significant correlation with glycaemic status and need more research and randomized controlled trials. Collectively, findings from our study particularly emphasize the need to control hyperglycemia and identify vulnerable groups of breast cancer patients who might benefit from interventions to improve glycaemic control.

e13083 Background: This study investigates the concordance between the 21-gene recurrence score assay, Oncotype DX (ODX), and the 70-gene signature MammaPrint (MP) in a single academic center and evaluates their correlation with breast cancer outcomes. We previously reported a discordance between MP and ODX results; here, we present a 10-year follow-up survival data. Methods: This prospective cohort study included eighty-six consecutive patients between 2012-2014 with node-negative, hormone receptor-positive breast cancer whose tumor samples were tested using ODX. Based on ODX recurrence scores (RS), patients were treated with either a chemotherapy plus hormonal therapy group or a hormonal therapy-alone group. All patients were per standard practices at our institution. MP was subsequently performed on all samples, classifying patients as either low-risk (MP-L) or high-risk (MP-H). ODX risk classification was defined as intermediate/high risk (ODX-H) for RS ≥ 26 in postmenopausal and ≥ 16 in premenopausal patients (As defined by the TAILORx trial, the addition of chemotherapy to endocrine therapy resulted in an absolute risk reduction of 1.6% in distant recurrence-free survival), and otherwise low risk (ODX-L) (ODX ≤ 26 in postmenopausal or ≤ 15 in premenopausal). Results: In the overall population, the 10-year overall survival (OS), disease recurrence-free survival (DRFS), and breast cancer-free interval (BCFI) were 93%, 91%, and 86%, respectively. Patients classified as ODX-H had lower survival rates (OS: 88%, DRFS: 86%, BCFI: 84%) compared to MP-H patients (OS: 92%, DRFS: 89%, BCFI: 87%). Patients classified as ODX-L had numerically better outcomes than MP-L patients (OS: 100%, DRFS: 97%, BCFI: 89%) compared to (OS: 94%, DRFS: 92%, BCFI: 86%). Approximately 29% of ODX-L patients were classified as MP-H, yet these patients demonstrated favorable long-term outcomes. Conclusions: Despite the limitations of a small sample size, our findings suggest that for patients with node negative hormonal receptor positive breast cancer ODX predicts better prognosis and response to chemotherapy than MP. Future prospective randomized trials directly comparing different genomic assays are warranted to optimize risk stratification and treatment decisions. Breast cancer outcomes based on genomic assay risk classification. Genomic assay / outcomes ODX MP High (n = 51) Low (n = 35) High (n = 37) Low (n = 49) OS 88% 100% 92% 94% DRFS 86% 97% 89% 92% BCFI 84% 89% 87% 86%

Breast cancer is the most common cancer affecting women globally with an estimated 2.3 million new cases in 2020. In Nigeria, it constitutes about 12% of all new cancers and 25% of all cancers in women. The risk factors of breast cancer include both non-modifiable and modifiable factors. There are clinical and biological differences between patients with pre-menopausal and post-menopausal breast cancer. This study aims to evaluate the differences in risk factors, disease presentation and tumour characteristics between premenopausal and postmenopausal breast cancer patients. This is a 2-year prospective cross-sectional study conducted at the University of Port Harcourt Teaching Hospital between 1st January 2021 and 31st December 2022. All consecutive patients who presented with breast cancer that was histologically confirmed and gave informed consent were included in the study. Patients were divided into two groups which are pre-menopausal and post-menopausal based on their menopausal status. Relevant data were extracted and recorded in a data extraction form. Analysis was done using Statistical Product and Service Solution version 26. One hundred and thirty-three patients were recruited for the study. Seventy (52.6%) of them were pre-menopausal and 63 (47.4%) were post-menopausal. Their ages were from 19 to 78 with a mean of 46.94 ± 11.93. The peak age was 41-50 years and 30.8% of the patients were within this age range. Only late age at first pregnancy was significantly associated with pre-menopausal breast cancer. Similar risk factors and tumour characteristics with a higher prevalence of triple-negative breast cancer were found in both groups but late age at first pregnancy occurred significantly in pre-menopausal breast cancer patients.

Background: The therapeutic effect of tamoxifen in adjuvant treatment of hormone receptor positive breast cancer might be impaired in patients with cytochrome P450 2D6 (CYP2D6) genotypes that predispose to decreased formation of potent anti-estrogenic tamoxifen metabolites. However, previous studies have shown inconsistent findings in this regard. In light of two recent studies failing to show an impact of CYP2D6 genotype on outcome in postmenopausal patients, we hypothesized that deficient CYP2D6 might be of greater importance in premenopausal patients with high levels of circulating estrogen. We therefore aimed to study the effect of CYP2D6 activity in both pre- and postmenopausal patients who were adherent to tamoxifen treatment for at least one year. Methods: 382 patients, from a population-based cohort of unselected breast cancer patients that were prescribed adjuvant tamoxifen for five years, constituted the base of the study. Information on menopausal status, tumor characteristics, treatment data including compliance and outcome was retrieved from medical records. Comprehensive CYP2D6 genotyping was performed and functionally translated into constitutive, metabolic activity. Results: In patients adherent to tamoxifen for at least one year (n = 313) there was an association of reduced CYP2D6 activity (≤50% of normal) to both recurrence (p = 0.02) and breast cancer-specific mortality (p = 0.03). In a multivariable analysis including CYP2D6 activity, age at diagnosis, tumor size, lymph node status, grade, adjuvant chemotherapy and concomitant use of CYP2D6 inhibitors, CYP2D6 remained an independent predictor of recurrence (HR = 0.39, 95% CI: 0.18–0.85, p = 0.02) and breast cancer specific survival (HR = 0.33, 95% CI 0.12–0.90, p = 0.03). Gradually decreasing CYP2D6 activity paralleled increasing risk of recurrence and breast cancer related mortality. The effect of CYP2D6 derived mainly from premenopausal patients with an association to both recurrence (p = 0.01) and breast cancer specific survival (p = 0.04). There was no such association in the postmenopausal group. Conclusion: In a prospectively collected cohort of tamoxifen-treated breast cancer patients, an association between CYP2D6 genotype and outcome was evident in patients that were adherent to tamoxifen treatment for at least a year. Importantly, this effect derived from premenopausal patients only. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr PD10-09.

156P The impact of Ki-67 on prognosis and chemotherapy benefit in breast cancer patients with ER-positive/HER2-negative micrometastatic disease in sentinel lymph nodes: A register-based cohort study

In 1989 it was suggested that the timing of surgery during follicular or corpus luteum phase of the menstrual cycle could substantially influence the survival time in premenopausal breast-cancer patients [1]. Several researchers analysed their data, but in general they could not confirm this observation. Nevertheless, two other reports in that series found some influence of the time of surgery during menstrual cycle on prognosis, although, they suggested different time periods as favourable [8, 9]. The purpose of this study was to investigate the effect of timing of surgery in a study population which was much larger than the previous studies. All premenopausal patients with primary breast cancer who had been operated at one clinic between 1st of January 1980 and 31st of December 1990 were considered eligible for the study. Based on the day of surgery during the menstrual cycle all patients were grouped according to three proposed categories and to an additional one which consisted of the favourable days from the three proposed categories. We investigated the effects of several prognostic factors and of the timing of surgery on three endpoints: recurrence free survival, distant disease free survival, and overall survival. The traditional prognostic factors had effects in agreement with the literature. Of the different categories for timing of surgery none had a significant influence; the strongest in univariate analysis had a p-value of 0.10 and the trend was in the opposite direction to the one proposed in the literature. These results did not change in multivariate analysis with the Cox model. Timing of surgery does not have an important effect on the prognosis of breast cancer patients. Incorporating other results from the literature, we conclude that it has at most a weak effect. At present there is no need to incorporate the day of menstrual cycle in the planning of surgery for premenopausal breast cancer patients.

33 Background: Tumor size is a clinicopathologic factor often used in early stage breast cancer (EBC) management to estimate prognosis and make decisions about therapy. While in general, small tumors have a lower chance of recurring than large tumors, some patients with small tumors have poor outcomes. The 21-gene breast cancer assay (OncotypeDX) yields a Recurrence Score result that predicts the 10-yr risk of distant recurrence (DR) and the likelihood of chemotherapy (CT) benefit in patients (pts) with ER+ EBC. This study reviews the clinical evidence and experience of the 21-gene assay in subcentimeter (subCM) tumors and shows that the Recurrence Score is more reflective of the underlying tumor biology. Methods: A meta-analysis of Genomic Health validation and supportive studies reporting Recurrence Score result and tumor size was conducted in order to describe the distribution of Recurrence Score results. Results: There were 10 GHI-sponsored studies (7,094 pts) that presented Recurrence Score results as a function of tumor size. The studies varied in the recorded tumor sizes, ranging from &lt; = 0.5 cm to &gt; 5 cm. Four studies specifically examined the distribution of Recurrence Score results in subCM tumors and identified a total of 629 pts out of 2,912 pts (21.6%) that fit the size criteria of &lt; 1cm. A broad distribution of score results was observed in subCM tumors in the four studies combined: 61% low, 25% int, 15% high. Conclusions: These results demonstrate that not all pts with subCM tumors have low risk disease, and that the 21-gene assay can help inform the risk of DR more precisely as well as predict the likelihood of CT benefit. Approximately 40% of pts had intermediate or high score results, suggesting an increased potential for DR and CT benefit. The clinical implications of this meta-analysis are that size doesn’t tell the whole story. There is underlying biology reflected in the Recurrence Score that can better inform the treatment decision for pts with ER+ EBC. [Table: see text]

Background: Serum protein profiles have been investigated frequently to discover predicted or prognostic biomarkers for breast cancer. Our previous studies have shown that serum protein peak 3144m/z is significantly elevated in metastatic ovarian cancer and gastric cancer. The receiver operating characteristic (ROC) curve obtained from metastatic ovarian cancer patients for differentially expressed protein peak 3144m/z showed when the cut-off value is 1.15, the sensitivity and specificity would be 65.4% and 91.4% respectively. Therefore, we investigated whether serum protein peak 3144m/z could be used as a potential prognostic tool for postmenopausal breast cancer, taking into account clinicopathological features. Methods: Two hundred and two postmenopausal breast cancer patients from June 2006 to December 2009 were involved in this retrospective study at Zhejiang Cancer Hospital. Menopausal status of the cases was obtained through examination of the medical records. The histopathological type, lymph node metastasis, and hormone receptor status of the cases were determined by pathologists. All patients underwent conventional postsurgical treatment (chemotherapy, radiotherapy, endocrinotherapy and target therapy) and the serum samples were collected before treatment. Serum level of protein peak 3144m/z was assessed by surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS). Prognostic factors (lymph node metastasis status, stage, hormone receptor status and molecular subtype) were compared across subgroups of patients depending on the protein peak 3144m/z levels. Cox proportional hazards regression was used for statistical analysis. Results: The precentage of cases with higher 3144m/z protein peak were 32.7%(66/202) in postmenopausal breast cancer patients. The serum protein peak 3144m/z was positively related to lymph node metastasis. However, there were no significant correlations between serum protein peak 3144m/z and other clinicopathological features, such as hormone receptor status, molecular subtype, clinical stage, pregnancy times and abortion history. Importantly, it was shown that patients with higher protein peak 3144m/z had significantly poorer overall survival compared with patients with lower serum protein peak 3144m/z (P = 0.0053). Furthermore, Cox multivariate regression analysis also revealed that protein peak 3144m/z was an independent prognostic factor in postmenopausal breast cancer patients (P = 0.008). Conclusions: The protein peak 3144m/z was a poor prognostic factor in postmenopausal breast cancer patients. Further prospective and longitudinal studies are needed to evaluate whether serum protein peak 3144m/z could be used as a prognostic tool in postmenopausal breast cancer patients monitoring and management. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P2-10-06.