Extensive Intraductal Component (EIC) Predicts for Locoregional Recurrence in HER2-Positive Patients Undergoing Breast Conserving Therapy

69 Background: Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer subtype is an adverse prognostic factor, it is unclear whether there are differences in outcomes according to the type of locoregional treatment used in this population. This study compared locoregional recurrence and survival outcomes in women with node-negative, HER2-positive breast cancer treated with Breast Conserving Therapy (BCT) versus Modified Radical Mastectomy (MRM). Methods: Independent datasets from the BC Cancer Agency (BCCA) and the Massachusetts General Hospital (MGH) were pooled and analyzed. Study subjects included 748 patients between 2003-2009 with pT1-2, N0, M0 Her2+ breast cancer, treated with BCT or MRM. Standard clinico-pathologic factors were analyzed. Kaplan-Meier locoregional recurrence (LRR), breast cancer specific survival (BCSS) and overall survival (OS) were compared between cohorts treated with BCT vs. MRM. Multivariable analysis (MVA) with Cox regression modeling was performed to evaluate the prognostic significance of type of locoregional treatment on outcomes. Results: Median follow-up time was 4.2 years for BCCA and 6.0 years for MGH. Comparison of clinico-pathologic factors according to type of locoregional treatment found that patients treated with MRM had higher proportions of grade 3 histology (69% vs. 60%, p = 0.004) and PR-negative disease (56% vs. 44%, p = 0.008) and lower rates of endocrine therapy (51% vs. 64%, p <0.001) and herceptin therapy (50% vs. 57%, p = 0.04). There were no significant differences between BCT and MRM groups in 5-year Kaplan-Meier LRR (2.0% vs. 1.7%, p=0.88), BCSS (97.2% vs. 96.1%, p=0.70), and OS (95.5% vs. 93.4%, p=0.19). On MVA, BCT and MRM were associated with similar LRR, BCSS, and OS. The only factor associated with reduced OS was T2 disease (HR 3.1, p=0.01). Conclusions: In this multi-institutional study, no significant outcome differences were found among women with T1-2 N0, HER2-positive breast cancer treated with BCT or MRM. Breast conserving therapy is safe in this population, providing high rates of locoregional control and survival equivalent to mastectomy.

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Differences in Risk Factors for Local and Distant Recurrence After Breast-Conserving Therapy or Mastectomy for Stage I and II Breast Cancer: Pooled Results of Two Large European Randomized Trials

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.6.1688 ◽

2001 ◽

Vol 19 (6) ◽

pp. 1688-1697 ◽

Cited By ~ 395

Author(s):

Adri C. Voogd ◽

Maja Nielsen ◽

Johannes L. Peterse ◽

Mogens Blichert-Toft ◽

Harry Bartelink ◽

...

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Vascular Invasion ◽

Breast Conservation ◽

Breast Conserving Therapy ◽

Distant Recurrence ◽

Extensive Intraductal Component ◽

Distant Disease ◽

Increased Risk ◽

Intraductal Component

PURPOSE: Risk factors for local and distant recurrence after breast-conserving therapy and mastectomy were compared to define guidelines for the decision making between both treatments. PATIENTS AND METHODS: The data of two randomized clinical trials for stage I and II breast cancer patients were pooled. The total number of patients in the study was 1,772, of whom 879 underwent breast conservation, and 893, modified radical mastectomy. Representative slides of the primary tumor were available for histopathologic review in 1,610 cases (91%). RESULTS: There were 79 patients with local recurrence after breast-conservation and 80 after mastectomy, the 10-year rates being 10% (95% confidence interval [CI], 8% to 13%) and 9% (95% CI, 7% to 12%), respectively. Age no more than 35 years (compared with age >60: hazard ratio [HR], 9.24; 95% CI, 3.74 to 22.81) and an extensive intraductal component (HR, 2.52; 95% CI, 1.26 to 5.00) were significantly associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion was predictive of the risk of local recurrence, irrespective of the type of primary treatment (P < .01). Tumor size, nodal status, high histologic grade, and vascular invasion were all highly significant predictors of distant disease after breast-conserving therapy and mastectomy (P < .01). Age no more than 35 years and microscopic involvement of the excision margin were additional independent predictors of distant disease after breast-conserving therapy (P < .01). CONCLUSION: Age no more than 35 years and the presence of an extensive intraductal component are associated with an increased risk of local recurrence after breast-conserving therapy. Vascular invasion causes a higher risk of local recurrence after mastectomy as well as after breast-conserving therapy and should therefore not be used for deciding between the two treatments.

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Locoregional Recurrence and Survival Outcomes by Type of Local Therapy and Trastuzumab Use Among Women with Node-Negative, HER2-Positive Breast Cancer

Annals of Surgical Oncology ◽

10.1245/s10434-014-3767-6 ◽

2014 ◽

Vol 21 (11) ◽

pp. 3490-3496 ◽

Cited By ~ 8

Author(s):

David J. Peterson ◽

Pauline T. Truong ◽

Betro T. Sadek ◽

Cheryl S. Alexander ◽

Bradley Wiksyk ◽

...

Keyword(s):

Breast Cancer ◽

Locoregional Recurrence ◽

Local Therapy ◽

Survival Outcomes ◽

Her2 Positive ◽

Node Negative ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

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Optimization of Taste-Masked (–)-Oleocanthal Effervescent Formulation with Potent Breast Cancer Progression and Recurrence Suppressive Activities

Pharmaceutics ◽

10.3390/pharmaceutics11100515 ◽

2019 ◽

Vol 11 (10) ◽

pp. 515 ◽

Cited By ~ 4

Author(s):

Tajmim ◽

Siddique ◽

El Sayed

Keyword(s):

Breast Cancer ◽

Cancer Progression ◽

Locoregional Recurrence ◽

Virgin Olive Oil ◽

Xenograft Model ◽

Taste Masking ◽

Control Group ◽

Placebo Control ◽

Her2 Positive ◽

Mouse Xenograft Model

S-(–)-Oleocanthal (OC), a naturally occurring phenolic secoiridoid exclusively found in extra-virgin olive oil (EVOO), is a potential nutraceutical therapeutic for inflammation, neurodegenerative diseases, and many malignancies, especially breast cancer (BC). The oral delivery of OC is challenging because of its irritative, bitter, and pungent taste and exceptional chemistry, including two reactive aldehydes, phenolic, and ester groups. OC irritation did not correlate with CO2-induced irritation, and hence, OC was not exerting generalized acid-sensing irritation. The objective of this study was to develop an effervescent formulation of OC with an effective CO2-induced masked taste maintaining the efficacy against the estrogen receptor (ER) and HER2 positive BC. Several ratios of acid and carbonate sources were screened, and five effervescent formulations EF1-EF5 were selected and prepared based on their pH and effervescence time. OC formulations were characterized using differential scanning calorimetry, FT-IR spectroscopy, and scanning electron microscopy analyses. OC formulations exhibited acceptable flowability and effervescence time. Based on physical characteristics and improved OC release, formulation EF-2 was selected for subsequent studies. EF-2 showed effective OC taste masking, as suggested by electronic artificial tongue and mouse preference tests. EF-2 suppressed more than 70% of the hormone and HER2-positive BT-474 BC cell growth in a nude mouse xenograft model. Furthermore, EF-2 demonstrated significant inhibition of BT-474 tumor cell locoregional recurrence after primary tumor surgical excision. EF-2-treated mouse sera had significantly reduced CA 15-3 levels, the human BC recurrence marker, compared to the placebo control group at the end of the study. These results highlight the potential of the OC formulation EF-2 as a prospective nutraceutical for the control and prevention of ER+/HER+ BC progression and locoregional recurrence.

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Outcomes and Predictive Factors for Salvage Therapy After Locoregional Recurrence Following Breast Conserving Therapy With Neoadjuvant Chemotherapy

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2012.07.486 ◽

2012 ◽

Vol 84 (3) ◽

pp. S188

Author(s):

D.C. Weksberg ◽

P.K. Allen ◽

K.E. Hoffman ◽

E.A. Strom ◽

R. Shah ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Predictive Factors ◽

Salvage Therapy ◽

Locoregional Recurrence ◽

Breast Conserving Therapy

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Survival after locoregional recurrence in patients after breast cancer surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.141 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 141-141

Author(s):

T. Osako ◽

R. Nishimura ◽

Y. Okumura ◽

R. Tashima ◽

Y. Toyozumi ◽

...

Keyword(s):

Breast Cancer ◽

Multivariate Analysis ◽

Prognostic Factors ◽

Primary Tumor ◽

Locoregional Recurrence ◽

Distant Metastases ◽

Breast Conserving Therapy ◽

Breast Cancer Surgery ◽

Systemic Metastasis

141 Background: The purpose of this study was to investigate factors for survival after locoregional recurrence in patients who underwent mastectomy or breast-conserving therapy (BCT) for primary breast cancer in our hospital. Methods: Out of 3,332 patients operated on from 1989 to 2008, 50 patients had chest wall recurrences after mastectomy (CWR), 40 patients had regional nodal recurrences (RNR), and 24 patients had ipsilateral breast tumor recurrences (IBTR) from 1997 to 2008. To investigate the prognostic factors for survival after locoregional recurrence, we conducted uni- and multivariate analyses of these cases. Results: The median follow-up time was 49.2 months. The 5-year survivals after recurrence of the patients with CWR, RNR and IBRT were 52%, 28%, and 68%, respectively. And the 10-year survivals were 15%, 0%, and 62%, respectively. Furthermore, the 5-year distant metastasis-free survivals were 24%, 13%, and 59%, respectively. In a multivariate analysis of the patients with CWR, type of recurrent nodules (diffuse/single, RR 21.0, p= 0.001), pT (T3 or 4 /T1, RR 11.4, p=0.01), pN (N3/N0, RR 15.5, p= 0.03), Ki67 of primary tumor (>50%/<20%, RR6.7, p=0.02) and ER of the primary tumor (+ / -, RR 2.6, p = 0.02) were independent prognostic factors. In a multivariate analysis of RNR, the method of first line salvage therapy (local /local + systemic, RR 16.1, p = 0.01) was only an independent prognostic factor. In the cases of IBTR, there were no independent prognostic factors for survival after recurrence. Conclusions: Although CWR developed distant metastases within 5 years, the survival depended upon the several biological factors. RNR developed distant metastases within a few years and provided poor prognosis. These suggested that RNR would be the first appearance of systemic metastasis not local disease. In contrast, IBTR provided better prognosis and a salvage treatment cured about 60% of the patients.

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