Letrozole Is More Effective Neoadjuvant Endocrine Therapy Than Tamoxifen for ErbB-1– and/or ErbB-2–Positive, Estrogen Receptor–Positive Primary Breast Cancer: Evidence From a Phase III Randomized Trial

2001 ◽  
Vol 19 (18) ◽  
pp. 3808-3816 ◽  
Author(s):  
Matthew J. Ellis ◽  
Andrew Coop ◽  
Baljit Singh ◽  
Louis Mauriac ◽  
Antonio Llombert-Cussac ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tyrosine Kinases ◽  
Primary Breast Cancer ◽  
Breast Conservation ◽  
Growth Factor Receptor ◽  
Tamoxifen Resistance ◽  
Breast Conserving Surgery ◽  
Phase Iii ◽  
Neoadjuvant Endocrine Therapy ◽  
Double Blinded

PURPOSE: Expression of ErbB-1 and ErbB-2 (epidermal growth factor receptor and HER2/neu) in breast cancer may cause tamoxifen resistance, but not all studies concur. Additionally, the relationship between ErbB-1 and ErbB-2 expression and response to selective aromatase inhibitors is unknown. A neoadjuvant study for primary breast cancer that randomized treatment between letrozole and tamoxifen provided a context within which these issues could be addressed prospectively. PATIENTS AND METHODS: Postmenopausal patients with estrogen– and/or progesterone receptor–positive (ER+ and/or PgR+) primary breast cancer ineligible for breast-conserving surgery were randomly assigned to 4 months of neoadjuvant letrozole 2.5 mg daily or tamoxifen 20 mg daily in a double-blinded study. Immunohistochemistry (IHC) for ER and PgR was conducted on pretreatment biopsies and assessed by the Allred score. ErbB-1 and ErbB-2 IHC were assessed by intensity and completeness of membranous staining according to published criteria. RESULTS: For study biopsy-confirmed ER+ and/or PgR+ cases that received letrozole, 60% responded and 48% underwent successful breast-conserving surgery. The response to tamoxifen was inferior (41%, P = .004), and fewer patients underwent breast conservation (36%, P = .036). Differences in response rates between letrozole and tamoxifen were most marked for tumors that were positive for ErbB-1 and/or ErbB-2 and ER (88% v 21%, P = .0004). CONCLUSION: ER+, ErbB-1+, and/or ErbB-2+ primary breast cancer responded well to letrozole, but responses to tamoxifen were infrequent. This suggests that ErbB-1 and ErbB-2 signaling through ER is ligand-dependent and that the growth-promoting effects of these receptor tyrosine kinases on ER+ breast cancer can be inhibited by potent estrogen deprivation therapy.

Axillary Metastasis with Occult Primary Breast Cancer

2017 ◽  
Author(s):  
Anne Kuritzky ◽  
Laila Khazai ◽  
Roberto Diaz ◽  
Christine Laronga
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Breast Conservation ◽  
Radical Mastectomy ◽  
Clinical Trial Data ◽  
Breast Conserving Surgery ◽  
Endocrine Treatment ◽  
Axillary Lymph ◽  
Axillary Metastasis ◽  
Cancer Breast

The identification of an axillary metastasis in the absence of a primary breast cancer can pose a diagnostic and therapeutic dilemma. The clinician should first use more sensitive imaging modalities, such as breast magnetic resonance imaging, to attempt to find the primary index lesion. If the primary cancer remains occult and the molecular markers are consistent with a breast origin, then the recommended treatment includes multimodality therapy including surgery, chemotherapy/endocrine treatment, and radiation. Historically, the modified radical mastectomy was the standard of practice. Recently, in the era of improved adjuvant therapies, breast-conserving surgery with irradiation is also being considered. Multiple retrospective reviews have shown no difference in survival or recurrence with these two surgical pathways. However, due to the rare nature of this clinical presentation, no multiinstitutional or prospective clinical trial data are available.  Key words: axillary lymph node dissection, axillary metastasis, breast cancer, breast conservation, local recurrence, occult primary tumor, radiotherapy 

Axillary Metastasis with Occult Primary Breast Cancer

2017 ◽  
Author(s):  
Anne Kuritzky ◽  
Laila Khazai ◽  
Roberto Diaz ◽  
Christine Laronga
Keyword(s):  
Breast Cancer ◽  
Primary Breast Cancer ◽  
Breast Conservation ◽  
Radical Mastectomy ◽  
Clinical Trial Data ◽  
Breast Conserving Surgery ◽  
Endocrine Treatment ◽  
Axillary Lymph ◽  
Axillary Metastasis ◽  
Cancer Breast

The identification of an axillary metastasis in the absence of a primary breast cancer can pose a diagnostic and therapeutic dilemma. The clinician should first use more sensitive imaging modalities, such as breast magnetic resonance imaging, to attempt to find the primary index lesion. If the primary cancer remains occult and the molecular markers are consistent with a breast origin, then the recommended treatment includes multimodality therapy including surgery, chemotherapy/endocrine treatment, and radiation. Historically, the modified radical mastectomy was the standard of practice. Recently, in the era of improved adjuvant therapies, breast-conserving surgery with irradiation is also being considered. Multiple retrospective reviews have shown no difference in survival or recurrence with these two surgical pathways. However, due to the rare nature of this clinical presentation, no multiinstitutional or prospective clinical trial data are available.  Key words: axillary lymph node dissection, axillary metastasis, breast cancer, breast conservation, local recurrence, occult primary tumor, radiotherapy 

scholarly journals Radiotherapy and Adjuvant Trastuzumab in Operable Breast Cancer: Tolerability and Adverse Event Data From the NCCTG Phase III Trial N9831

2009 ◽  
Vol 27 (16) ◽  
pp. 2638-2644 ◽  
Author(s):  
Michele Y. Halyard ◽  
Thomas M. Pisansky ◽  
Amylou C. Dueck ◽  
Vera Suman ◽  
Lori Pierce ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Incidence ◽  
Early Stage ◽  
Growth Factor Receptor ◽  
Breast Conserving Surgery ◽  
Phase Iii ◽  
Cardiac Events ◽  
Adjuvant Trastuzumab ◽  
Significant Difference

Purpose To assess whether trastuzumab (H) with radiotherapy (RT) increases adverse events (AEs) after breast-conserving surgery or mastectomy. Patients and Methods Patients with early-stage resected human epidermal growth factor receptor 2 (HER-2) –positive breast cancer (BC) were randomly assigned to doxorubicin (A) and cyclophosphamide (C), followed by weekly paclitaxel (T; AC-T-H or AC-TH-H). RT criteria (with or without nodal RT) were postlumpectomy breast or (optional) postmastectomy chest wall. RT of internal mammary nodes was prohibited. RT commenced within 5 weeks after T, concurrently with H. Analysis included 1,503 irradiated patients for RT-associated AEs across treatment arms. Rates of cardiac events (CEs) with and without RT were compared within arms. Results No significant differences among arms were found in incidence of acute skin reaction, pneumonitis, dyspnea, cough, dysphagia, or neutropenia. A significant difference occurred in incidence of leukopenia, with higher rates for AC-T-H versus AC-T (odds ratio = 1.89; 95% CI, 1.25 to 2.88). At a median follow-up of 3.7 years (range, 0 to 6.5 years), RT with H did not increase relative frequency of CEs regardless of treatment side. The cumulative incidence of CEs with AC-T-H was 2.7% with or without RT. With AC-TH-H, the cumulative incidence was 1.7% v 5.9% with or without RT, respectively. Conclusion Concurrent adjuvant RT and H for early-stage BC was not associated with increased acute AEs. Further follow-up is required to assess late AEs.

Co-expression of ER-beta and HER2 associated with poorer prognosis in primary breast cancer

2009 ◽  
Vol 32 (3) ◽  
pp. 250 ◽  
Author(s):  
Wen-sheng Qui ◽  
Lu Yue ◽  
Ai-ping Ding ◽  
Jian Sun ◽  
Yang Yao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Differentiation ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Univariate Analysis ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Er Alpha

Purpose: To assess the prognostic value of co-expression of estrogen receptor (ER)-beta and human epidermal growth factor receptor 2 (HER2) in primary breast cancer patients in China. Methods: Tumour specimens from 308 patients undergoing surgery for primary breast cancer were evaluated. Expression of ER-beta and HER-2 was investigated by the immunohistochemistry. Results: 123 patients (40%) were ER-beta positive and 58 (18.5 %) were HER2 positive. Among the 58 HER2 positive patients, 44 were ER-beta positive and 14 were ER-beta negative. ER-beta positive was associated with HER2 positive (75.9%, P=0.018) as well as ER-alpha positive (79.7%, P=0.023), poor cell differentiation (77.2% grade 2 or 3, P=0.010) and menopause age < 45 yr (55.3%, P=0.031). HER2 positive was associated with poor cell differentiation (93.1%, P=0.001), ?3cm tumour size (67.2%, P=0.011). Conclusion: Both ER-beta positive and HER2 positive status was associated with poorer overall survival (OS) by univariate analysis. In both HER2 positive and HER2 negative subgroups, ER-beta positive was associated with poorer distant disease free survival (DDFS) but not OS, which implied that ER-beta might relate to metastasis in breast cancer.

scholarly journals Comparison of metabolic changes after neoadjuvant endocrine and chemotherapy in ER-positive, HER2-negative breast cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ho Hyun Ryu ◽  
Sei Hyun Ahn ◽  
Seon Ok Kim ◽  
Jeong Eun Kim ◽  
Ji sun Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metabolic Profile ◽  
Fasting Glucose ◽  
Medical Center ◽  
Mean Value ◽  
Metabolic Changes ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Neoadjuvant Endocrine Therapy ◽  
The Mean

AbstractSurvival of breast cancer patients has improved, and treatment-related changes regarding metabolic profile deterioration after neoadjuvant systemic treatment (NST) become important issues in cancer survivors. We sought to compare metabolic profile changes and the neutrophil-to-lymphocyte ratio (NLR) between patients undergoing neoadjuvant chemotherapy (NCT) and neoadjuvant endocrine therapy (NET) 3 years after the treatment. In a prospective, randomized, phase III trial which compared 24 weeks of NCT with adriamycin and cyclophosphamide followed by docetaxel and NET with goserelin and tamoxifen (NEST), 123 patients in the Asan Medical Center were retrospectively reviewed to evaluate metabolic changes, such as body mass index (BMI), blood pressure (BP), total cholesterol (TC), fasting glucose, and the NLR. The mean age of patients was 42 years. The changes in BMI, serum glucose, and TC during NST and after 3 years were significantly different between NCT and NET. The proportion of overweight + obese group and the mean BMI were significantly increased during NCT (26.6% to 37.5%, 22.84 kg/m2 to 23.87 kg/m2, p < 0.05), and these attributes found to have normalized at the 3-year follow-up. In the NET group, BMI changes were not observed (p > 0.05, all). There were no differences in changes over time among in the Hypertension group during NCT and NET (p = 0.96). The mean value of serum TC and fasting glucose significantly increased (< 0.05, both) during NCT and decreased 3 years after NCT (p < 0.05); however, no significant changes were observed in the NET group. The NLR was increased from 1.83 to 3.18 after NCT (p < 0.05) and decreased from 1.98 to 1.43 (p < 0.05) after NET. Compared with minimal metabolic effect of NET, NCT worsens metabolic profiles, which were recovered over 3 years. The NLR was increased after NCT but decreased after NET.

scholarly journals Sequential Versus Concurrent Trastuzumab in Adjuvant Chemotherapy for Breast Cancer

2011 ◽  
Vol 29 (34) ◽  
pp. 4491-4497 ◽  
Author(s):  
Edith A. Perez ◽  
Vera J. Suman ◽  
Nancy E. Davidson ◽  
Julie R. Gralow ◽  
Peter A. Kaufman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Growth Factor Receptor ◽  
Disease Free Survival ◽  
Standard Of Care ◽  
Phase Iii ◽  
P Value ◽  
Sequential Administration ◽  
Taxane Chemotherapy

Purpose NCCTG (North Central Cancer Treatment Group) N9831 is the only randomized phase III trial evaluating trastuzumab added sequentially or used concurrently with chemotherapy in resected stages I to III invasive human epidermal growth factor receptor 2–positive breast cancer. Patients and Methods Patients received doxorubicin and cyclophosphamide every 3 weeks for four cycles, followed by paclitaxel weekly for 12 weeks (arm A), paclitaxel plus sequential trastuzumab weekly for 52 weeks (arm B), or paclitaxel plus concurrent trastuzumab for 12 weeks followed by trastuzumab for 40 weeks (arm C). The primary end point was disease-free survival (DFS). Results Comparison of arm A (n = 1,087) and arm B (n = 1,097), with 6-year median follow-up and 390 events, revealed 5-year DFS rates of 71.8% and 80.1%, respectively. DFS was significantly increased with trastuzumab added sequentially to paclitaxel (log-rank P < .001; arm B/arm A hazard ratio [HR], 0.69; 95% CI, 0.57 to 0.85). Comparison of arm B (n = 954) and arm C (n = 949), with 6-year median follow-up and 313 events, revealed 5-year DFS rates of 80.1% and 84.4%, respectively. There was an increase in DFS with concurrent trastuzumab and paclitaxel relative to sequential administration (arm C/arm B HR, 0.77; 99.9% CI, 0.53 to 1.11), but the P value (.02) did not cross the prespecified O'Brien-Fleming boundary (.00116) for the interim analysis. Conclusion DFS was significantly improved with 52 weeks of trastuzumab added to adjuvant chemotherapy. On the basis of a positive risk-benefit ratio, we recommend that trastuzumab be incorporated into a concurrent regimen with taxane chemotherapy as an important standard-of-care treatment alternative to a sequential regimen.

scholarly journals Is It Contralateral Axillary Metastasis or Occult Breast Cancer: A Confusing Case Report

2015 ◽  
Vol 8 (3) ◽  
pp. 498-502 ◽  
Author(s):  
Yong Gi Son ◽  
Woon Won Kim ◽  
Ki Hoon Kim ◽  
Jin Soo Kim
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Growth Factor Receptor ◽  
Immunohistochemical Analysis ◽  
Breast Conserving Surgery ◽  
Left Breast ◽  
Lymph Node Biopsy ◽  
Adjuvant Radiation ◽  
Axillary Lymph ◽  
Axillary Metastasis

We report the case of a 43-year-old woman with primary left breast cancer presenting metastatic lymphadenopathy in the contralateral axilla. This patient represents a diagnostic and therapeutic challenge because primary breast cancer, occult contralateral breast cancer, and extra-mammary primary lesion can all be the source of the contralateral axillary metastasis. Left breast-conserving surgery, left sentinel lymph node biopsy, right breast mass excision, and right axillary lymph node dissection were performed. Immunohistochemical analysis revealed that the left breast cancer specimen was positive for estrogen receptor (ER) and progesterone receptor (PR), but negative for human epidermal growth factor receptor 2 (HER2). In contrast, the right axillary lymphadenopathy specimen was negative for ER and PR, but positive for HER2. Further investigation revealed no evidence of occult primary cancers or extra-mammary tumors. After surgical intervention, the patient was treated with adjuvant chemotherapy, adjuvant radiation therapy, and targeted therapy with trastuzumab. Two years after diagnosis, she is free of disease and presently being treated with tamoxifen.

scholarly journals Response to Induction Neoadjuvant Hormonal Therapy Using Upfront 21-Gene Breast Recurrence Score Assay—Results From the SAFIA Phase III Trial

2021 ◽  
pp. 811-819
Author(s):  
Khalid AlSaleh ◽  
Heba Al Zahwahry ◽  
Adda Bounedjar ◽  
Mohammed Oukkal ◽  
Ahmed Saadeddine ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Interim Analysis ◽  
Growth Factor Receptor ◽  
Recurrence Score ◽  
Phase Iii ◽  
Phase Iii Trial ◽  
Hormone Sensitivity ◽  
Epidermal Growth ◽  
Breast Recurrence

PURPOSE Luminal, human epidermal growth factor receptor 2–negative breast cancer represents the most common subtype of breast malignancies. Neoadjuvant strategies of operable breast cancer are mostly based on chemotherapy, whereas it is not completely understood which patients might benefit from neoadjuvant hormone therapy (NAHT). MATERIALS AND METHODS The SAFIA trial is a prospective multicenter, international, double-blind, neoadjuvant phase III trial, using upfront 21-gene Oncotype DX Breast Recurrence Score assay (recurrence score [RS] < 31) to select operable luminal human epidermal growth factor receptor 2–negative patients, for induction hormonal therapy HT (fulvestrant 500 mg with or without goserelin) before randomly assigning responding patients to fulvestrant 500 mg (with or without goserelin) plus either palbociclib (cyclin-dependent kinase 4/6 inhibitor) or placebo. The objectives of this interim analysis were to assess the feasibility of upfront RS determination on core biopsies in the Middle-East and North Africa region and evaluate the efficacy of induction NAHT in patients with an RS < 31. RESULTS At the time of this interim analysis, 258 patients with relative risk were accrued, including 202 patients (RS < 31% to 78.3%) treated with induction NAHT and 182 patients evaluable so far for response. The feasibility of performing the Oncotype DX assays on core biopsy specimens was optimal in 96.4% of cases. Overall, 93.4% of patients showed hormone sensitivity and no difference in NAHT efficacy was noticed between RS 0-10, 11-25, and 26-30. Interestingly, patients with high RS (26-30) showed a trend toward a higher major response rate ( P = .05). CONCLUSION The upfront 21-gene assay performed on biopsies is feasible in our population and has allowed us to select patients with high hormone sensitivity (RS < 31). This approach could be an alternative to upfront surgery without significant risk of progression, particularly during pandemic times.

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