Abstract P5-22-02: Surgical strategy after neoadjuvant therapy in patients with operable breast cancer can be optimized by knowledge of the level of agreement of measured tumor size on MRI after neoadjuvant therapy and final pathologic assessment

LBA506 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.

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Predictive factors of resistance to trastuzumab as neoadjuvant therapy in women with HER2-positive breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.26_suppl.168 ◽

2013 ◽

Vol 31 (26_suppl) ◽

pp. 168-168

Author(s):

Hiromitsu Jinno ◽

Tomomi Sato ◽

Maiko Takahashi ◽

Tetsu Hayashida ◽

Shigemichi Hirose ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Therapy ◽

Hormone Receptor ◽

Direct Sequencing ◽

Pik3ca Mutation ◽

Operable Breast Cancer ◽

Mechanisms Of Resistance ◽

Her2 Positive ◽

Pten Loss ◽

Hormone Receptor Positive

168 Background: Despite clinical usefulness of trastuzumab, intrinsic or acquired resistance to trastuzumab is a common clinical phenomenon. However, the mechanisms of resistance to trastuzumab have not been fully elucidated. The objective of this study was to determine the possible mechanisms of resistance to trastuzumab as neoadjuvant therapy in women with HER2-overexpressing operable breast cancer. Methods: Patients with operable breast cancer received 12 cycles of weekly paclitaxel plus weekly trastuzumab before surgery. All tumors were HER2-positive by immunohistochemistry (IHC) or fluorescence in situ hybridization. Expressions of ER, PgR, Ki67, PTEN, phosphorylated IGF-1R (pIGF-1R) and MUC4 were performed by IHC in core needle biopsy samples at baseline. PIK3CA mutation status was evaluated by sequencing of PIK3CA exons 9 and 20 using PCR amplification and direct sequencing. Results: Thirty-seven patients were enrolled and assessable for clinical and pathologic responses. The pCR rate was 48.6% (18/37). Negative, moderate and strong membranous expression of MUC4 was observed in 3 (8.1%), 18 (48.6%) and 12 (32.4%) patients, respectively. Membranous staining for pIGF1-R was negative in 24 (64.9%) patients. PTEN loss was observed in 33.3% (8/24) of the tumor examined. PIK3CA sequence analysis of the 13 tumors identified 2 mutations in exon 20 and 2 mutations in exon 9, corresponding to a PIK3CA mutation frequency of 30.8%. MUC4 status did not affect the pCR rate. Although membranous pIGF1-R expression did not affect pCR rate in hormone receptor-positive patients (66.7% vs. 50.0%), hormone receptor-positive patients with positive membranous pIGF1-R tended to show higher pCR rate compared with negative pIGF1-R (41.2% vs. 0%). PTEN loss and/or PIK3CA mutation were not significantly associated with pCR rate. Conclusions: These data indicate that aberrant downstream signaling caused by loss of PTEN and/or PIK3CA mutation, alternative signaling from IGF-1R and masking with MUC4 were not important mechanisms of resistance to trastuzumab.

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Prognostic Significance of Nottingham Histologic Grade in Invasive Breast Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2007.15.5986 ◽

2008 ◽

Vol 26 (19) ◽

pp. 3153-3158 ◽

Cited By ~ 274

Author(s):

Emad A. Rakha ◽

Maysa E. El-Sayed ◽

Andrew H.S. Lee ◽

Christopher W. Elston ◽

Matthew J. Grainge ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Size ◽

Strong Predictor ◽

Prognostic Significance ◽

Disease Free Survival ◽

Operable Breast Cancer ◽

Histologic Grade ◽

Grading System ◽

Consecutive Series ◽

Staging Systems

Purpose The three strongest prognostic determinants in operable breast cancer used in routine clinical practice are lymph node (LN) stage, primary tumor size, and histologic grade. However, grade is not included in the recent revision of the TNM staging system of breast cancer as its value is questioned in certain settings. Materials and Methods This study is based on a large and well-characterized consecutive series of operable breast cancer (2,219 cases), treated according to standard protocols in a single institution, with a long-term follow-up (median, 111 months) to assess the prognostic value of routine assessment of histologic grade using Nottingham histologic grading system. Results Histologic grade is strongly associated with both breast cancer–specific survival (BCSS) and disease-free survival (DFS) in the whole series as well as in different subgroups based on tumor size (pT1a, pT1b, pT1c, and pT2) and LN stages (pN0 and pN1 and pN2). Differences in survival were also noted between different individual grades (1, 2, and 3). Multivariate analyses showed that histologic grade is an independent predictor of both BCSS and DFS in operable breast cancer as a whole as well as in all studied subgroups. Conclusion Histologic grade, as assessed by the Nottingham grading system, provides a strong predictor of outcome in patients with invasive breast cancer and should be incorporated in breast cancer staging systems.

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A population model to predict progression free survival in breast cancer patients treated with neoadjuvant chemotherapy ñ vaccines based on tumour growth inhibition metrics.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12114 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12114-e12114

Author(s):

Belen P.Solans ◽

Diego Salas ◽

Marta Abengozar ◽

Luis Javier Pina ◽

Arlette Elizalde ◽

...

Keyword(s):

Breast Cancer ◽

Prognostic Factors ◽

Neoadjuvant Chemotherapy ◽

Tumor Growth ◽

Growth Inhibition ◽

Neoadjuvant Therapy ◽

Tumor Size ◽

Clinical Benefit ◽

Progression Free Survival ◽

Free Survival

e12114 Background: Breast cancer (BC) is the most commonly diagnosed malignancy in women. Neoadjuvant chemotherapy selects patients with optimal pathological responses and increases tumorectomy versus total mastectomy. Changes in tumor size (CTS) are related to an early clinical benefit and to Progression Free Survival (PFS) and Overall Survival (OS) in BC patients. Thus, the identification of new prognostic factors in the neoadjuvant scenario is crucial. Objectives:To assess the link between tumor growth inhibition metrics (TGI) and progression free survival (PFS) based on data obtained from BC patients with neoadjuvant therapy Methods: Data were obtained from 218 patients with BC treated at the University Clinic of Navarra, diagnosed from January 2008 to February 2016, with a median age of 49 years (range 25 to 84). Classification of molecular subtypes was based on IHC and found as follows: Her2 (6%), LA ( 23%), LB ( 36%), LB-Her2 (10%) and TN ( 25%). Patients were treated with ddECx 4 followed Docetaxel x 4. Her2 patients had therapy with Trastuzumab. 18% of the patients (LB and TN) received vaccination with dendritic cells. Data were analysed under the population approach with NONMEN 7.3. A model accounting for the dynamics of tumor growth and antitumor effect of the neoadjuvant therapy was developed. The model describes tumor size as the sum of the longest diameters of target lesions as a function of time and drug exposure. A PFS model was developed to describe the PFS time distribution as a function of covariates Results: The TGI was able to individually and accurately describe the tumor shrinkage. Vaccinated patients had an increased shrinkage rate of 36% (p < 0.001) than those who were not (p < 0.001). PFS (months) was best described by a Weibull model, and greater tumor size at diagnosis (p < 0.05), smaller CTS (p < 0.05) and TN subtype (p < 0.001) were identified as poor prognostic factors Conclusions: A PFS model that uses a model-based estimate of tumor growth to predict the PFS of BC patients receiving neoadjuvant therapy has been developed. This model helps to gain early understanding of potential clinical benefit to facilitate go/no-go decision making.

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Which patient characteristics drive treatment decisions in elderly patients with early stage hormone receptor–positive breast cancer?

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.538 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 538-538

Author(s):

Sacha Satram-Hoang ◽

Carolina M. Reyes ◽

Alisha Stein ◽

Khang Q. Hoang ◽

Faiyaz Momin ◽

...

Keyword(s):

Breast Cancer ◽

Elderly Patients ◽

Neoadjuvant Therapy ◽

Tumor Size ◽

Hormone Receptor ◽

Stage I ◽

Genomic Testing ◽

Lower Grade ◽

Risk Of Death ◽

Hormone Receptor Positive

538 Background: Hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) is the most common biologic subtype of breast cancer (BC). We examined treatment patterns and outcomes associated with adjuvant or neoadjuvant therapy among elderly patients (pts) in the US. Methods: The analysis included 18,470 first primary HR+HER2- BC pts from the linked SEER-Medicare database. Pts were diagnosed with Stage I-III disease between 1/1/2007-12/31/2011, ≥66 years, continuously enrolled in Medicare Parts A/B in the year prior to diagnosis, enrolled in Part D in the year after diagnosis, and underwent BC surgery ≤6 months after diagnosis. Time-varying Cox proportional hazards regression assessed overall survival adjusting for pt characteristics. Date of last follow-up was 12/31/2013. Results: There were 13,670 (74%) pts treated with hormonal therapy +/- chemotherapy and 4,800 (26%) untreated. Compared to treated pts, untreated pts were older, had earlier stage, lower grade, smaller tumors, poorer performance, higher comorbidity, and less genomic testing for risk of recurrence (p<0.0001). In a multivariate analysis, increasing age, stage, tumor size, tumor grade, comorbidity score and poor performance were significantly associated with higher mortality risks, while use of genomic testing was associated with a lower risk of death. The Cox model showed a 48% higher risk of death in untreated compared to treated pts (HR=1.48; 95% CI=1.35-1.61). Even in a subset of 8,967 pts with stage I disease, tumor size <2.0cm and grade 1/2; untreated pts had a 22% higher risk of death compared to treated pts (HR=1.22; 95% CI=1.05-1.41). Conclusions: Patients who are older with favorable disease characteristics (earlier stage, smaller tumor, lower grade) are less likely to be treated and have a higher risk of death compared to pts who received adjuvant or neoadjuvant therapy. The unmet need among elderly BC pts remains, suggesting that age should not deter guideline-based therapy. [Table: see text]

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Economic evaluation of neoadjuvant chemotherapy for operable breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12637 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12637-e12637

Author(s):

Nicholas Zdenkowski ◽

Shefi Mary D'Silva ◽

Kenny Lawson ◽

Penny Reeves ◽

Frances M. Boyle

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Neoadjuvant Therapy ◽

Value Of Information ◽

Cost Effective ◽

Operable Breast Cancer ◽

Information Analysis ◽

Neoadjuvant Systemic Therapy ◽

Surgery First ◽

The Impact

e12637 Background: Neoadjuvant chemotherapy is widely and increasingly used for patients with operable breast cancer that is large or highly proliferative. Advantages include downstaging of the breast and. axilla, post-neoadjuvant salvage treatments for poor responders, surgical and reconstruction planning, prognostication and to give time for genetic testing. After neoadjuvant therapy, treatment options may change. We aimed to determine the financial impact to the health system, of neoadjuvant chemotherapy compared with surgery first. Methods: A literature search identified data on the probability of receiving certain investigations and treatments, and associated outcome probabilities for neoadjuvant and surgery-first patients. Published health utility results were used. These data were incorporated into a decision analytic economic model. A cost-utility analysis was undertaken, with sensitivity analyses to evaluate the impact of uncertainties in the data. Pricing was based on publicly available costings of investigations and treatment in Australian Dollars (AUD). A value of information analysis was undertaken to determine the value of further research to reduce uncertainty in results. Results: Expected costs for neoadjuvant vs surgery first differed by $77. Neoadjuvant therapy showed higher effectiveness that surgery first (QALY 0.708 vs 0.698 respectively. The average cost per QALY of neoadjuvant therapy was $7,232 AUD (ca. $4825 USD), below the threshold of $50,000 per QALY. In a sensitivity analysis, neoadjuvant therapy dominated when axillary dissection rate was lower than 60% and postmastectomy reconstruction rate was more than 27%. These factors had the greatest impact on results, which were otherwise robust. Probabilistic sensitivity analysis found that neoadjuvant therapy was cost-effective 71% of the time at a willingness-to-pay threshold of $50,000 per QALY. Value of information analysis found that primary research into treatment probabilities and outcome utilities is needed to validate these results. Conclusions: Neoadjuvant systemic therapy is a potentially cost-effective treatment. However, primary contemporary data in directly comparable patient populations is needed, including the impact of post-neoadjuvant systemic therapy.

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