Bh Son

Cardiac dose reduction during tangential breast irradiation using deep inspiration breath hold: a dose comparison study based on deformable image registration.

BackgroundRadiation therapy (RT) for a left-sided breast cancer often involves some incidental exposure of the heart and increase in the rate of major coronary events. One method to reduce the dose to the heart during a tangential breast irradiation is the deep inspiration breath hold (DIBH) technique. Our department adopted DIBH for selected left breast cancer patients with a maximum cardiac distanceu2009≥u200910xa0mm. We evaluated the effect of the DIBH on cardiac dose compared to normal free breathing (FB). The secondary objective of our present study was to use modeled risk estimates to quantify the risk of coronary events after RT with DIBH.Methods and materialsThirty-two patients who underwent RT with DIBH at our hospital were retrospectively analyzed. For each patient, two computed tomography (CT) scans were acquired, FB-CT and DIBH-CT. Using a deformable image registration tool, the target volume was deformed from DIBH-CT to FB-CT, and conventional tangential treatment planning was performed, focusing on the equality of target coverage between the two plans. Doses to the heart, left anterior descending (LAD) artery, and ipsilateral lung were assessed.ResultsBy using DIBH, the average mean heart dose was reduced from 724.1xa0cGy to 279.3 (pu2009<u20090.001). The relative heart volume irradiated with 10xa0Gy–50xa0Gy was consistently reduced. The mean dose to the LAD coronary artery was reduced from 4079.1xa0cGy to 2368.9xa0cGy (pu2009<u20090.001). The ipsilateral lung volume receiving 20xa0Gy or more and 40xa0Gy or more was reduced by 2.2 % in both cases. Estimated risks of coronary events at 10xa0years were 4.03 and 2.55 % for RT with FB and DIBH, respectively (pu2009<u20090.001).ConclusionsThe use of DIBH during RT of the left-sided breast considerably reduces the doses delivered to the heart and LAD artery with similar target coverage. For the current study patients, the probability of major coronary events was reduced with DIBH.

Tissue microarray-based study of patients with lymph node-negative breast cancer shows that HER2/neu overexpression is an important predictive marker of poor prognosis

BACKGROUNDnDespite good prognosis in most cases of lymph node (LN)-negative breast cancer, individual patients may have markedly different clinical outcomes. Here, we investigated the prognostic significance of HER2/neu overexpression in these tumors.nnnMATERIALS AND METHODSnWe employed a tissue microarray to examine HER2/neu overexpression by immunohistochemical staining in 359 consecutive patients diagnosed with LN-negative breast cancer, who underwent surgery from January 1993 to December 1998.nnnRESULTSnHER2/neu overexpression was detected in 81 of 359 (23.1%) patients. The 10-year disease-free survival (DFS) values (81.2% versus 61.8%, P value 0.000) and overall survival (OS) rates (85.7% versus 63.9%, P value 0.000) were significantly different between cases with HER2/neu-negative or HER2/neu-positive tumors. After multivariate analysis, HER2/neu status and tumor size were identified as independent prognostic factors for 10-year OS. Moreover, HER2/neu overexpression was significantly associated with poorer clinical outcomes in an intermediate-risk group identified by the St Gallen classification (10-year DFS, 79.6% versus 61.8%, P value 0.000; 10-year OS, 84.7% versus 63.9%, P value 0.000).nnnCONCLUSIONSnOur results show that HER2/neu overexpression is an important independent prognostic factor for LN-negative breast cancer cases and support the theory that more intensive adjuvant chemotherapy is required in the population with HER2/neu overexpression.

Expression of FOXM1 and related proteins in breast cancer molecular subtypes

Forkhead box (FOX) proteins constitute an extended family of transcriptional regulators. FOXM1 is ubiquitously expressed in cells undergoing proliferation, and overexpression of FOXM1 is associated with poor prognosis in various malignant tumours. FOXM1 and FOXO3a are often transcriptionally antagonistic. FOXO3a plays a critical tumour‐suppressive role in breast cancer. FOXO activity is modulated by its acetylation status, which is regulated by class III histone deacetylases (sirtuins; also known as SIRTs). This study evaluated the role of FOX proteins and their regulators in each molecular subtype of breast cancer. Immunohistochemical expressions of FOXM1, FOXO3a, SIRT1 and SIRT6 were evaluated in tissue microarray blocks containing 688 consecutive breast cancer samples. Mean expression levels were used to categorize tumours according to the expression of each protein (high or low). High expression of FOXM1 was significantly correlated with high SIRT1 and SIRT6 expression, higher histologic grade and triple‐negative breast cancer (TNBC). High expression of nuclear FOXO3a and nuclear SIRT1 was correlated with a lower histologic grade and the hormone receptor‐positive/HER2‐negative subtype. In survival analysis, FOXM1 was an independent adverse prognostic factor for disease‐free and overall survival in the hormone receptor‐positive/HER2‐negative subtype but not in the HER2‐positive subtype or TNBC. In conclusion, although high FOXM1 expression was noted in the TNBC subtype, it had no prognostic impact in TNBC. However, it had prognostic significance in the hormone receptor‐positive/HER2‐negative subtype.

Meeting Highlights: The First Korean Breast Cancer Treatment Consensus Conference

The first Korean Breast Cancer Treatment Consensus Conference Expert Panel reviewed and endorsed new evidence on aspects of local and regional therapies and diagnostic procedures that support the conservative application of results from recent clinical trials. This conference clarified the barriers that limit the application of recent clinical trial results, such as questions about level of evidence, differences between the setting of clinical trials and that of daily clinical practice, and medical necessities and environment. Detailed decisions recommended for the treatment and diagnosis, according to the from the consensus conference, are recorded including details of the votes. These recommendations differed in the degree of support for clinical consideration of disease extent and host factors, medical necessities, and environment.

Phase II trial of neoadjuvant letrozole and lapatinib in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2)-positive breast cancer [Neo-ALL-IN]: Highlighting the TILs, ER expressional change after neoadjuvant treatment, and FES-PET as potential significant biomarkers

PurposeNeo-ALL-IN (NCT 01275859) is a single-center, phase II study aimed to evaluate the efficacy and safety profiles of neoadjuvant letrozole plus lapatinib, as well as potential biomarkers, in postmenopausal women with ER- and HER2-positive (ER+HER2+) breast cancer.MethodsPostmenopausal ER+HER2+ breast cancer of stages II–III was eligible. Daily 2.5xa0mg letrozole plus 1500xa0mg lapatinib were administered for 18–21xa0weeks before surgery. Clinical responses were assessed by palpation with caliper, breast ultrasonography, mammogram, and/or MRI. Biologic samples were collected for biomarker analyses at three time points (baseline, day 14, and before surgery). Baseline fluorine-18 fluorodeoxyglucose and fluorine-18 fluoroestradiol PET-CT scans were performed.ResultsAmong 24 patients enrolled, 17 (70.8xa0%) completed planned neoadjuvant treatment, whereas 7 prematurely terminated the treatment and proceeded to surgery because of toxicity or progression; 2 patients showed definite progression, and 2 showed clinical regrowth by palpation regardless of minimal response. All patients eventually underwent breast cancer surgery. Toxicities were generally mild mostly within grades 1–2 except prolonged or recurrent grade 3 liver toxicities in 3 patients (13.6xa0%) regardless of sequential dose reduction, which finally led to discontinuation of treatment. The overall clinical response rates were 62.5xa0% (nxa0=xa015) including 1 CR in breast. However, no pathologic CR (ypT0–is N0) was achieved. SUVmax lower than 5.5 in baseline FES PET-CT (pxa0=xa00.007), baseline TILs over 20xa0% (pxa0=xa00.026), and decreased IHC ER Allred score after neoadjuvant treatment (pxa0=xa00.021) were significantly associated with adverse clinical response.ConclusionsWhen this chemo-free, combination neoadjuvant therapy with letrozole and lapatinib is given for Asian postmenopausal ER+HER2+ breast cancer, TILs, change of ER expression following neoadjuvant treatment, and SUVmax in baseline FES-PET are to be considered potential biomarkers in these patients.

Triple Negative Breast Cancer Has a Worse Prognosis within 3 Years after Treatment Compared to Non-Triple Negative Breast Cancer.

Background Triple negative breast cancers (TNBC) become known as poor prognosis generally. Our purpose was to compare the clinical features and outcomes for TNBC with other subtypes of breast cancers in Korea. Methods We included 2,907 patients who diagnosed breast cancer and treated at Asan Medical Center from 2003 to 2005. Clinical and pathologic parameters, disease-free survival (DFS) and overall survival (OS) were compared between patients with TNBC and non-TNBC. All features were reviewed throughout medical records retrospectively. Results 622 patients (21.4%) had TNBC. TNBC patients was associated with younger age, larger size, positive nodal involvement, overweight, family history, elevation of CaAg15-3, high tumor grade, positive p53 compared non-TNBC. The patients were followed for a median of 54 months (range 1-76 months). Relapse-free survival was 86.3% and 92.6% for TNBC and non-TNBC, respectively, with significant difference (P Conclusions TNBC has a worse prognosis than non-TNBC patients, but this effect is limited within 3 years after diagnosis. The most competent prognostic factor of recurrence and death for TNBC is a nodal status. We plan that perform analysis for prognosis according to hormone receptor and HER-2 receptor status sooner. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4044.

Long-term Survival Outcomes of Primary Breast Cancer in Women With or Without Preoperative Magnetic Resonance Imaging: A Matched Cohort Study

AIMSnTo investigate whether preoperative magnetic resonance imaging (MRI) in patients with primary breast cancer is predictive of disease-free (DFS) and overall survival and to determine the prognostic factors indicating survival.nnnMATERIALS AND METHODSnThis retrospective study was approved by the institutional review board and the requirement for informed consent was waived. From 2009 to 2010, 828 women with primary breast cancer and preoperative MRI were matched with 1613 women without such imaging. Patients were matched with regards to 25 patient and tumour-related covariates. A Cox proportional hazards model was used to investigate the time to recurrence and to estimate the hazard ratio for preoperative MRI. Log-rank tests and Cox proportional hazards survival analysis were carried out on total recurrence DFS and overall survival in the unmatched datasets.nnnRESULTSnIn total, 799 matched pairs were available for survival analysis. The MRI group showed a tendency towards better survival outcome; however, there were no significant differences in DFS and overall survival. Age at diagnosis (DFS hazard ratioxa0=xa00.98; overall survival hazard ratioxa0=xa01.04), larger tumour size (DFS hazard ratioxa0=xa01.01; overall survival hazard ratioxa0=xa01.02), triple negative breast cancer (DFS hazard ratioxa0=xa02.64; overall survival hazard ratioxa0=xa03.44) and the presence of lymphovascular invasion (DFS hazard ratioxa0=xa02.12; overall survival hazard ratioxa0=xa02.70) were independent significant variables for worse DFS and overall survival.nnnCONCLUSIONnPreoperative MRI did not result in an improvement in a patients outcome. Age at diagnosis, tumour size, molecular subtype and lymphovascular invasion were significant independent factors affecting both DFS and overall survival.

Abstract P1-14-02: Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In]: First efficacy and safety report

Purpose Neo-ALL-In (NCT 01275859) is a single center, prospective study aimed to evaluate the recruitment feasibility, efficacy and safety profiles as well as biologic features of neoadjuvant letrozole plus lapatinib in postmenopausal women with ER and HER2 positive breast cancer. Methods Postmenopausal women with stage IIA to IIIB ER and HER-2 positive breast cancer were eligible. Patients received combination therapy of letrozole 2.5 mg orally daily plus lapatinib 1,500 mg orally daily for 18-21 weeks before surgery. Clinical responses were assessed by clinical palpation, ultrasonography (US), mammography and/or MRI. Tissue and/or blood samples were collected for analysis of biomarkers at three time points (baseline, day 15, and before surgery). Baseline Fluorine-18 Fluorodeoxyglucose ( 18 F-FDG) and Fluorine-18 Fluoroestradiol ( 18 F-FES) PET-CT imagings were obtained. Results Among twenty-four patients enrolled, 22 patients underwent surgery while 1 patient is currently on neoadjuvant therapy and the other patient is waiting for surgery. Among 22 patients completed surgery, 16 patients (72.7%) completed planned neoadjuvant letrozole and lapatinib, whereas 3 patients (13.6%) prematurely terminated the treatment and proceeded to surgery due to minimal clinical response or progression. Except grade 3 liver toxicities revealed in 3 patients (13.6%), which resulted in sequential dose reduction and discontinuation, adverse events were mainly grades 1 to 2 (Skin, 83.3%; GI, 77.3%), and these were generally tolerable with excellent compliance. Overall clinical response rates including complete and partial response was 72.7% (n=16), and pathologic complete response in breast (pCR; yp T 0-is ) was 4.5% (n=1). In analyses of biomarkers thus far, 81.8% of patients showed stationary expression of HER-2, 54.5% of patients showed decrease in Ki-67 expression, and 27.3% of patients showed increase in ER expression from baseline to surgery by immunothistochemistry (IHC) staining. Decreased expression of ER after surgery by IHC staining was significantly correlated with poor clinical response (p=0.004). However, no significant differences in baseline SUVmax in FDG-PET were found between responders and non-responders (8.8 VS 10.7, p=0.53). Conclusion This chemo-free combination neoadjuvant therapy was feasible, with comparable efficacy outcomes and manageable toxicities profiles. Updated data on 18 F-FES PET-CT and biomarkers will be provided. Citation Format: Ji Hyun Park, Myoung Joo Kang, Jin-Hee Ahn, Jeong Eun Kim, Kyung Hae Jung, Gyung-Yub Gong, Hee Jin Lee, Byung-Ho Son, Sei-Hyun Ahn, Hak-Hee Kim, Hee Jung Shin, Dae-Hyuk Moon, Sung-Bae Kim. Neoadjuvant letrozole and lapatinib is feasible in Asian postmenopausal women with estrogen receptor (ER) and human epidermal growth factor receptor-2 (HER-2) positive breast cancer [Neo-All-In]: First efficacy and safety report [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 P1-14-02.

Abstract P6-06-24: Intact p53 can predict more hormonal therapy benefit in invasive breast cancer: Evaluation of interactions between immunohistochemical p53 status and adjuvant therapy

Background: To confirm the prognostic and predictive values of p53 accumulation, particularly in invasive breast cancer patients sorted according to subgroup based on immunohistochemical hormone receptor (HR) and HER2 status. Methods: A total of 15,598 immunohistochemical data for p53, ER, PgR, and HER2 were retrospectively retrieved from the web-based database of the Korean Breast Cancer Society. Overall survival (OS) and breast cancer-specific survival (BCSS) were calculated and compared with the Kaplan-Meier method with log-rank test. Multivariate analyses were performed using a stratified Cox proportional hazard regression model. A model evaluating interactions between p53 and both hormonal therapy and chemotherapy was used to determine the treatment benefit from both modalities. Results: Prognostic value of p53 was most significant in the HR+/HER2- subgroup for OS and BCSS, with hazard ratios of 1.44 (95% CI, 1.08-1.93) and of 1.47 (95% CI, 1.09-1.99). The hazard ratios for p53 overexpression had borderline significance in the HR+/HER2+, and were invalid in the HR-/HER2+ and HR-/HER2- subgroups. The model with interaction terms revealed that hormonal therapy significantly interacts with p53 status (p = .002 and .007 for OS and BCSS), resulting in an insignificant prognostic value of p53 status (p = .268 and .296 for OS and BCSS). An interaction between chemotherapy and p53 status was not found in this model. Conclusion: p53 overexpression has independent prognostic value, particularly in the HR+/HER2- invasive breast cancer, which is most likely caused by differential treatment benefits from hormonal therapy depending on p53 status. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-24.

Abstract P3-12-05: Clinical features and outcomes of leptomeningeal metastasis in patients with breast cancer: a single center experience

Background: Leptomeningeal metastasis (LM) is one of the major problems in managing metastatic breast cancer because of LM typically carries a devastating prognosis and often represents a terminal event. We analyzed the clinical features and outcomes of LM in patients with breast cancer. Methods: We retrospectively reviewed the medical records of patients who were diagnosed with LM from breast cancer between 2002 and 2012 at Asan Medical Center. Results: Of the 95 LM patients by cytologically proven (n = 81) or radiologically diagnosed (n = 14), 57 (60%) had an ECOG performance status (PS) ≥ 3, and the median age was 47 years (range, 26–72 years). The patients were diagnosed with LM after a median of 10.3 months (95% CI, 5.5–15.0 months) from the time of diagnosis of metastatic breast cancer. LM was present in 2 patients at the time of initial diagnosis. Twenty-three patients (24.2%) had isolated CNS metastasis, and 6 (6.3%) had only LM without any detectable metastasis sites. At the time of diagnosis of LM, 46 patients (48.4%) presented with coincidental failure of systemic disease control. Seventy-eight patients (82.1%) underwent intrathecal chemotherapy (methotrexate; n=78, thiotepa; n=11), resulting in one-third of cytologic negative conversion (n = 26), and 41 (43.2%) received systemic chemotherapy. The overall median survival time was 3.3 months (95% CI, 2.5–4.2 months) and 7.8% of the patients survived for more than 1 year. Overall survival tended to be better in patients who achieved cytologic negative conversion to intrathecal chemotherapy than those did not (median 4.5 months versus 3.2 months, P = 0.241). Overall survival was not different according to subtypes; hormone receptor (+), HER2 (+), and triple negative (median 3.6 months, 3.3 months, and 3.2 months, P = 0.937). Multivariate analysis demonstrated that ECOG PS ≥ 3 (HR = 2.09, 95% CI 1.21–3.58, P = 0.007), coincidental failure of systemic disease control at LM (HR = 3.01, 95% CI 1.76–5.15, P P = 0.001) were independent factors associated with survival. Conclusions: The prognosis for patients with LM from breast cancer was still poor. Systemic chemotherapy in addition to intrathecal chemotherapy might confer a survival benefit, even after the detection of LM. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-12-05.