Role of clinical and histologic factors in decision making on adjuvant therapy of small HER2-positive breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11053-e11053
Author(s):  
Faisal Azam ◽  
Saif Yousif ◽  
Aarifah Aaseem ◽  
Eliyaz Ahmed
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Tumour Size ◽  
Screening Mammography ◽  
Her2 Positive ◽  
Node Negative ◽  
Er Positive ◽  
Her 2 ◽  
Er Status

e11053 Background: With increased use of screening mammography for breast cancer (BC), the incidence of small (T1a, b), node negative BC has increased. These cancers are considered low-risk and hence not offered adjuvant (adj) chemotherapy (CT). However, increasing retrospective studies suggest that outcomes in small node negative HER-2 positive BC might be worse than the HER-2 negative tumours of similar size. Current guidelines generally do not recommend adj CT and Trastuzumab (T) for small (T1 a, b) HER-2 positive tumours. As a part of our ongoing audit on the outcome of small HER -2 positive BC, we wished to determine the factors that oncologists consider in decision making on adj treatment of these tumours in the absence of clear guidelines. Methods: Patients (pts) with a diagnosis of node negative T1a, b, HER-2 positive BC treated across our cancer network, between Jan 2008 and Dec 2011, were identified from our electronic database. Results: A total 230 pts had stage T1, HER 2 +ve BC. Out of those 41(17%) pts had tumour size of < 1cm (13, 31%pts were T1a and 28, 74%pts wereT1b) and node negative disease. Median age was 55 years (29-84yrs). 33 Pts had BCS and 8 pts had mastectomy. All pts with BCS received adj radiotherapy and all pts who were ER positive received adj endocrine therapy. 21(51%) out of 41pts received adjuvant CT and T. All pts had anthracycline based CT. The clinical and pathological characteristics of pts who received adj CT and T were as follows; Median age- 50 (33-64years), grade 1- 1(4%), grade 2 – 9(43%), grade 3- 11(53%), LVI present- 2(9%), LVI absent- 7(34%), LVI unknown – 12(57%), ER positive- 16(76%), ER negative – 5(24%). None of the pts had recurred or died at the time of analysis of the data and longer follow up is needed for survival analysis. Conclusions: In the absence of clear guidelines on adj CT and T in node negative small HER-2 positive BC, the oncologists relied on the traditional factors such as grade, ER status in risk stratification and decision on adj therapy. Tumour grade was the most important factor but age and ER status were not discriminating factors in this study. Prospective randomised trials needed to clearly define the role of adj systemic therapy in this group of pts.

Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

2014 ◽  
Vol 32 (31) ◽  
pp. 3513-3519 ◽  
Author(s):  
Julia Bonastre ◽  
Sophie Marguet ◽  
Beranger Lueza ◽  
Stefan Michiels ◽  
Suzette Delaloge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Cost Effectiveness ◽  
Adjuvant Chemotherapy ◽  
Cost Effective ◽  
Gene Signature ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Life Years ◽  
Er Positive

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) –positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, −€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Conclusion Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC.

scholarly journals EP.TH.275The role of amino acid transporters SLC1A5 and SLC3A2 in primary breast cancer in older women

2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Ruth Parks ◽  
Lutfi Alfarsi ◽  
Andrew Green ◽  
Kwok-Leung Cheung
Keyword(s):  
Breast Cancer ◽  
Amino Acid ◽  
Older Women ◽  
Primary Breast Cancer ◽  
Tumour Size ◽  
Glutamine Metabolism ◽  
Amino Acid Transporters ◽  
Younger Women ◽  
Er Status

Abstract Aims Breast cancer in older women has more favourable biology, compared to younger women. Increased glutamine metabolism is a hallmark of cancer. The prognostic role of amino acid transporters involved with glutamine flux, SLC1A5 and SLC3A2, has been shown in breast cancer in younger women. This study aimed to investigate the role of SLC1A5 and SLC3A2 in breast cancer in older women as possible prognostic markers. Methods Surgical specimens were obtained from an existing series of 1,758 older women (≥70 years) with primary breast cancer, treated in a single institution with long-term (37+ years) follow-up. Of this cohort, 813 had primary surgical treatment. As part of previous work, it was possible to construct good quality tissue microarrays (TMAs) in 575 cases. Immunohistochemical staining for SLC1A5 and SLC3A2 was performed. H-score was considered as a continuous variable as well as using positivity cut-offs of ≥ 45 for SLC1A5 and ≥15 for SLC3A2, using X-tile software. Association between H-score and tumour size, grade, ER status, local-recurrence-free-survival (LRFS), overall survival (OS) and breast-cancer-specific-survival (BCSS) was investigated. Results No correlation was seen between neither marker and LRFS, OS, or BCSS in older women with breast cancer. Both markers were associated with high tumour grade and negative ER status (both p &lt; 0.001). Conclusions These findings are contrary to those found in younger women, where these amino acid transporters are associated with shorter BCSS. This may suggest that breast cancer in older women is less reliant on glutamine metabolism, which is consistent with an overall less aggressive phenotype.

Human Epidermal Growth Factor Receptor 2 Status Correlates With Lymph Node Involvement in Patients With Estrogen Receptor (ER) –Negative, but With Grade in Those With ER-Positive Early-Stage Breast Cancer Suitable for Cytotoxic Chemotherapy

2007 ◽  
Vol 25 (28) ◽  
pp. 4423-4430 ◽  
Author(s):  
John M.S. Bartlett ◽  
Ian O. Ellis ◽  
Mitch Dowsett ◽  
Elizabeth A. Mallon ◽  
David A. Cameron ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Nodal Metastasis ◽  
Breast Cancers ◽  
Node Negative ◽  
Tumor Pathology ◽  
Er Positive ◽  
Her 2 ◽  
Epidermal Growth ◽  
Grade 3

Purpose Human epidermal growth factor receptor 2 (HER-2) expression is associated with increased risk of high-grade disease, nodal metastasis, and absence of estrogen receptors (ERs) in early breast cancer. We tested interactions between ER and HER-2 to determine if they may modulate breast cancer nodal metastasis and proliferation. Patients and Methods Tumors from the Cancer Research UK Taxotere as Adjuvant Chemotherapy phase III trial were tested for HER-2 using current diagnostic procedures. ER status, progesterone status, clinicopathologic characteristics, and patient age were included in a logistic regression analysis to identify associations with HER-2 status (positive v negative). Results A total of 841 (23.6%) of 3,565 samples were HER-2 positive (3+ by immunohistochemistry or positive by fluorescent in situ hybridization). ER-negative tumors were more likely to be HER-2 positive than were ER-positive tumors (odds ratio [OR] = 1.87, ER negative v ER positive; P < .001). For ER-positive tumors, risk of HER-2 positivity increased by grade (OR = 7.6, grade 3 v grade 1; P < .001) but not nodal status (OR = 1.3, four or more positive nodes v node negative; P = .08). Conversely, ER negative node-positive tumors were markedly more frequently HER-2 positive than node-negative cases (OR = 3.05, four or more positive nodes v node negative; P < .001) but independent of grade (OR = 0.82, grade 3 v grade 1; P = .76). Conclusion In early breast cancer patients selected for cytotoxic chemotherapy, we identified significant interactions between HER-2 and ER expression that correlate with tumor pathology. In ER-positive breast cancers, HER-2 expression correlates with grade, not nodal metastasis. In ER-negative breast cancers, HER-2 expression correlates with increased nodal positivity, not grade. ER and HER-2 expression may modify tumor pathology via ER/HER-2–mediated cross talk.

scholarly journals Assessment of the predictive role of oestrogen and progesterone receptor status in breast cancer patients treated with neoadjuvant chemotherapy: A retrospective analysis for 689 patients

2020 ◽  
Author(s):  
Ying Ye ◽  
Rui Chen ◽  
Yong Fu ◽  
Yang Peng ◽  
Fanli Qu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Progesterone Receptor ◽  
Tumour Size ◽  
Tumour Response ◽  
Therapy Response ◽  
Breast Cancer Patients ◽  
Predictive Role ◽  
Her 2

Abstract Background : To explore the predictive indicators in hormone receptor (HR)-positive breast cancer (BC) patients receiving neoadjuvant chemotherapy (NACT) and to evaluate the value of quantitative oestrogen receptor (ER) and progesterone receptor (PR) in predicting tumour response. Methods : Six hundred eighty-nine BC patients with HR-positive status who were treated with anthracycline, epirubicin and taxane NACT treatment were retrospectively analysed. Clinical and pathological features of the patients were used to evaluate the response to NACT. Results : Patients with larger tumour sizes ( OR 1.657 CI 1.186-2.313 p=0.003 ), those who were in a premenopausal status ( OR 1.458 CI 1.039-2.045 p=0.029 ) and those with higher Ki67 levels ( OR 1.735 CI 1.231-2.444 p=0.002 ) exhibited a better therapy response. Among the patients in the postmenopausal subgroup, a lower pretreatment ER or PR expression were associated with a reduction in tumour size, and the cut-off values for ER and PR were 87.5% and 65%, respectively ( p=0.006 and p=0.05 ). Decreased expression of ER and PR was also observed after NACT treatment ( p=0.028 and p<0.001, respectively ) but played only a predictive role in the Her-2-negative subgroup; the cut-off values for decreased ER and PR were 17.5% and 26.5%, respectively ( p=0.044 and p<0.001 ). Conclusions : Semiquantified pretreatment HR expression can be used to predict the response of NACT in postmenopausal BC patients. Decreased ER and PR expression is also associated with a reduction in tumour size in Her-2-negative subtypes treated with NACT.

scholarly journals Prognostic and predictive value of low estrogen receptor expression in breast cancer

2017 ◽  
Vol 24 (2) ◽  
pp. 106 ◽  
Author(s):  
A. Bouchard-Fortier ◽  
L. Provencher ◽  
C. Blanchette ◽  
C. Diorio
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Hormonal Therapy ◽  
Proportional Hazards ◽  
Tumour Size ◽  
Survival Rates ◽  
Cox Proportional Hazards ◽  
Receptor Expression ◽  
Er Positive ◽  
Er Status

Purpose Anti-hormonal therapy (tamoxifen) is recommended for estrogen receptor (er)–positive breast cancer (bca); however, its effect on low-receptor cancers is unclear. We retrospectively evaluated the effect of adjuvant tamoxifen in patients with weakly er-positive bca.Methods We identified 2221 bca patients who had been er-tested by ligand-based assay (lba) during 1976–1995 and who had been treated and followed until 2008. Cox proportional hazards models adjusted for age, body mass index, tumour size, nodal status, surgery, and chemotherapy were used to assess the effect of er level on bca survival in patients who received tamoxifen.Results Overall, 17% (383) of patients were within 0–3 fmol/mg cytosol protein, and 12% (266) were within 4–9 fmol/mg cytosol protein. Patients with er levels of 0–3, 4–9, 10–19, 20–49, and 50 fmol/mg or more cytosol protein had 20-year bca survival rates of 56%, 56%, 63%, 71%, and 60% respectively. Of the 2221 patients studied, 661 (29.8%) received anti-hormonal therapy. Within the latter group, er levels of 0–3, 4–9, 10–19, 20–49, and 50 fmol/mg or more cytosol protein were associated with a hazard ratio for lower bca mortality: respectively, 1.00 (reference), 0.59 (p = 0.09), 0.19 (p < 0.0001), 0.26 (p < 0.0001), and 0.31 (p < 0.0001)—the risk reduction being significant only for er levels of 10 fmol/mg or more cytosol protein.Conclusions Tamoxifen use in bca patients with a weakly positive er status (4–9 fmol/mg cytosol protein), compared with those having higher er levels (≥10 fmol/mg cytosol protein), is not associated with a significantly lower bca-specific mortality. Our results do not support treatment with anti-hormonal therapy for bca patients with a weakly positive er status as identified by lba.

Role of Patient and Disease Factors in Adjuvant Systemic Therapy Decision Making for Early-Stage, Operable Breast Cancer: American Society of Clinical Oncology Endorsement of Cancer Care Ontario Guideline Recommendations

2016 ◽  
Vol 34 (19) ◽  
pp. 2303-2311 ◽  
Author(s):  
N. Lynn Henry ◽  
Mark R. Somerfield ◽  
Vandana G. Abramson ◽  
Kimberly H. Allison ◽  
Carey K. Anders ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Adjuvant Therapy ◽  
Lymphovascular Invasion ◽  
Early Stage ◽  
Oncotype Dx ◽  
Node Negative ◽  
Distant Relapse ◽  
American Society

Purpose An American Society of Clinical Oncology (ASCO) panel considered the Cancer Care Ontario (CCO) recommendations on the role of patient and disease factors in selecting adjuvant therapy for women with early-stage breast cancer for endorsement. Methods ASCO staff reviewed the CCO guideline for methodologic rigor, and an ASCO panel of content experts reviewed the content of the recommendations. CCO Recommendations For making decisions regarding adjuvant therapy, nodal status, tumor size, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2) status, tumor grade, and lymphovascular invasion are relevant; Oncotype DX score and Adjuvant! Online may be used as risk stratification tools; and age, menopausal status, and medical comorbidities should be considered. Chemotherapy should be considered for patients with positive lymph nodes, ER-negative disease, HER2-positive disease, Adjuvant! Online mortality greater than 10%, grade 3 lymph node–negative tumors (T > 5 mm), triple-negative (ER-negative, PgR-negative, HER2-negative) tumors, lymphovascular invasion positivity, or estimated distant relapse risk of greater than 15% at 10 years based on Oncotype DX recurrence score (RS). Chemotherapy may not be beneficial or required for small node-negative tumors (T < 5 mm) without high-risk features or for patients with HER2-negative, strongly ER-positive, and PgR-positive cancer with micrometastatic nodal disease, T less than 5 mm, or Oncotype DX RS with an estimated distant relapse risk of less than 15% at 10 years. ASCO Panel Conclusion The ASCO panel endorses the recommendations with minor suggested revisions and highlights three areas that warrant further consideration: tumor histology and adjuvant therapy recommendations, risk stratification tools and proposed Oncotype DX RS thresholds to guide decisions about chemotherapy, and patient factors in decision making.

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.

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