BCS Rate Research Articles

Efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin in neoadjuvant therapy for locally advanced triple-negative breast cancer: A prospective cohort study with propensity-matched analysis.

Optimizing neoadjuvant therapy for triple-negative breast cancer (TNBC) is still an urgent problem to be solved in the clinic. In this prospective cohort study, we investigated the efficacy and safety of apatinib combined with dose-dense paclitaxel and carboplatin (Apa+ddTCb) vs dose-dense paclitaxel plus carboplatin regimens alone (ddTCb) in neoadjuvant therapy for locally advanced TNBC. TNBC patients with clinical stage I-IIIC were enrolled to receive neoadjuvant Apa+ddTCb therapy. Enrolled patients who underwent surgery were matched with TNBC patients who received neoadjuvant ddTCb therapy by propensity score matching. 25 locally advanced TNBC patients were enrolled for neoadjuvant Apa+ddTCb therapy. The overall clinical ORR achieved 88.00% and DCR achieved 100.0% after 6 cycles. For 23 patients who received surgery, 69 TNBC patients who received neoadjuvant ddTCb therapy were matched. The pCR rate (60.9% vs 30.4%, P = .009) and the BCS rate (47.8% vs 21.7%, P = .016) were significantly improved in the Apa+ddTCb group. The incidence of adverse events, especially those related to antiangiogenic therapy, was higher in the Apa+ddTCb group. Further immunohistochemical analysis suggested that the expression levels of VEGF, EGFR, p-VEGFR2 and CK17 were significantly decreased after receiving neoadjuvant therapy in the Apa+ddTCb group, and the baseline CK17 expression level in non-pCR patients was significantly higher than those in the pCR patients. Progression-free survival was not reached yet. Apa+ddTCb regimen achieved an improved efficacy and acceptable adverse events compared with ddTCb regimen, which might be a promising strategy in the neoadjuvant therapy for locally advanced TNBC.

Demographic evaluation and outcome of the early breast cancer patients undergoing breast conservation surgery as the primary modality of management – A single institutional experience at a medical teaching hospital

The rates of BCS in the Indian subcontinent vary between 11% and 34%, as compared to the management of breast cancer in the west where the rates of BCS are as high as 70% in early breast cancer. All this has brought to light the need for evaluation of the best and the most functional and cosmetic surgeries that are available in the management of breast cancer especially when detected in the ver early stages. With all this in mind we decided to study the demographic evaluation and outcome of the early breast cancer patients undergoing breast conservation surgery as the primary modality of management at a medical teaching hospital.The study was done at the department of general surgery, oncosurgery, radiation oncology and medical oncology at Father Muller Medical College Hospital. All breast cancer patients underwent the following treatment regimen:- Surgery that included BCS with Axillary Dissection followed by neo adjuvant chemotherapy CFU regimen and then after completion of systemic chemotherapy 50-55 Gy of radiotherapy to the remaining breast with a tumor bed boost of 9-12 Gy in daily 2 Gy fractions for 5 days in a week over 5-6 weeks was given.In the present study new-found that the most common site in the breast for breast cancer was the superior - lateral quadrant of the 70 cases 56 cases 80% were in the superior - lateral quadrant. Common in this area. The most common histology seen in 67 cases 95.71% was infiltrating duct carcinoma. The median age was 45 years. 65 cases 92.86% had node-negative disease and 54 cases 77.14% tumors were hormone receptor-positive. One case developed isolated local recurrences which were managed surgically. None of the rest 69 cases of them had recurrence during follow up. The mean age was 44.75 with SD 8.8 years. The youngest was 28 years and the eldest was 63 years of age. In the 295 cases, we had 3 male cases, among those who had BCS all were females. We would like to conclude that whenever it is possible to conserve the breast every woman has to be given the option of breast conservation. It is also needed that the health care professionals and the primary health care physicians be sensitized to the need for effective clinical breast examination so that the rate of detection of early cancer be hastened and more women are offered the option of breast conservation.

PersonaLized neoAdjuvant Strategy ER Positive and HER2 Negative Breast Cancer TO Increase BCS Rate

PersonaLized neoAdjuvant Strategy ER Positive and HER2 Negative Breast Cancer TO Increase BCS Rate

Breast-conserving surgery versus mastectomy in young women with breast cancer in Asian settings.

BackgroundMastectomy rates among women with early breast cancer in Asia have traditionally been high. This study assessed trends in the surgical management of young women with early‐stage breast cancer in Asian settings. Survival in women treated with breast‐conserving surgery (BCS; lumpectomy with adjuvant radiotherapy) and those undergoing mastectomy was compared.MethodsYoung women (aged less than 50 years) newly diagnosed with stage I or II (T1–2 N0–1 M0) breast cancer in four hospitals in Malaysia, Singapore and Hong Kong in 1990–2012 were included. Overall survival (OS) was compared for patients treated by BCS and those who had a mastectomy. Propensity score analysis was used to account for differences in demographic, tumour and treatment characteristics between the groups.ResultsSome 63·5 per cent of 3536 women underwent mastectomy. Over a 15‐year period, only a modest increase in rates of BCS was observed. Although BCS was significantly associated with favourable prognostic features, OS was not significantly different for BCS and mastectomy; the 5‐year OS rate was 94·9 (95 per cent c.i. 93·5 to 96·3) and 92·9 (91·7 to 94·1) per cent respectively. Inferences remained unchanged following propensity score analysis (hazard ratio for BCS versus mastectomy: 0·81, 95 per cent c.i. 0·64 to 1·03).ConclusionThe prevalence of young women with breast cancer treated by mastectomy remains high in Asian countries. Patients treated with BCS appear to survive as well as those undergoing mastectomy.

Abstract P6-08-04: National trends in mastectomy for operable breast cancers treated with neoadjuvant chemotherapy

Abstract Objective: Although neoadjuvant chemotherapy (NAC) has not been shown to improve survival compared with adjuvant therapy for patients with operable invasive breast cancer (IBC), it is often used to allow more limited surgery in the breast and axilla without compromising local control. We sought to evaluate national trends in mastectomy among patients with operable breast cancer treated with NAC and to characterize the contribution of demographic and tumor characteristics to changing trends. Methods: We queried the National Cancer Database (NCDB) 2014 Participant User File for adult women who underwent surgery and received chemotherapy for unilateral T1-3N0-3M0 IBC diagnosed between 2010 and 2014. Surgery was classified as lumpectomy (BCS), unilateral mastectomy (UM) or bilateral mastectomy (BM). Molecular subtype was categorized according to ER, PR, and HER2 status. We used logistic regression to model surgery use (BM or UM vs BCS), adjusting for the following clinical covariates that were selected a priori: age, race/ethnicity, year of diagnosis, comorbidity score, metropolitan vs urban/rural residence, patient distance from treating facility, % with less than high school education (zip code based), insurance type, clinical stage, histology, and molecular subtype. As those who achieved pathologic complete response (pCR) after NAC should be ideal candidates for BCS, we also looked at this group separately. We then performed sensitivity analyses further controlling for region of the country and facility type, and for facility. Results: We identified 235,339 patients who fulfilled our inclusion criteria. Of these patients, 25.3% were treated with NAC. Rates of pCR increased from 33.3% in 2010 to 46.3% in 2014 (p<0.001). Rates of BCS increased from 37.0% in 2010 to 40.8% in 2014 (p<0.001). While rates of UM decreased from 43.3% in 2010 to 34.7% in 2014 (p<0.001), rates of BM with or without reconstruction increased from 19.7% in 2010 to 24.6% in 2014 (p<0.001). Rates of BM without immediate reconstruction remained stable over time, from 11.8% in 2010 to 11.5% in 2014. Among patients who received NAC, factors that were independently associated with both UM and BM (versus BCS) for both the entire cohort and those who achieved pCR included younger age, greater patient distance from facility, and higher clinical stage. Factors that were inversely associated with both UM and BM included black race and ductal histology. More recent year of diagnosis was inversely associated with UM and directly associated with BM. Asian race was associated with UM while non-Hispanic white race was associated with BM. Private or managed care insurance and higher area education were also associated with BM. These results were materially unchanged in sensitivity analyses. Conclusion: Rates of pCR have increased over time among patients with operable IBC treated with NAC. While the rate of UM has declined over time, the rate of BM has increased. Significant sociodemographic differences exist between women who undergo BCS, and women who undergo UM and BM. Further study of factors that influence surgical decision-making in the NAC setting is warranted. Citation Format: Pollom E, Qian Y, Dirbas F, Horst K, Tsai CJ. National trends in mastectomy for operable breast cancers treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-04.

National Trends in the Use of Neoadjuvant Chemotherapy for Hormone Receptor-Negative Breast Cancer: A National Cancer Data Base Study.

Neoadjuvant chemotherapy (NAC) downstages tumor size and nodal disease. This study evaluates national practice patterns of NAC use in hormone receptor-negative breast cancer. We identified patients in the National Cancer Data Base (NCDB) with hormone receptor-negative invasive breast cancer (2004-2012). Univariate and multivariable logistic regression was used to assess associations and trends across time. Of 171,985 patients, 130,723 (76.0%) received chemotherapy and 41,262 (24.0%) did not. Chemotherapy use was higher in young patients and higher T- and N-stage disease (all p<0.001). Of those patients treated with chemotherapy, 23,165 (17.7%) received NAC and 107,558 (82.3%) received adjuvant chemotherapy (AC). NAC use increased from 2004 to 2012 (13.0-23.5%; adjusted odds ratio [aOR] 1.42; p<0.001). Higher clinical T stage (ORs 3.63, 11.81, and 22.34 for cT2, cT3, and cT4a-c, respectively, vs. cT1) and cN+ disease (OR 2.86) [each p<0.001] were associated with NAC, as were younger patient age and better Charlson-Deyo comorbidity score. Furthermore, BCS rate was higher in the NAC group in cT2 and cT3 tumors (aOR 1.17 and 1.45, respectively; both p<0.001). In patients with cN+ disease, NAC converted 43.7% to pN0. Less extensive axillary surgery (one to five nodes removed) was more likely in cN+ patients treated with NAC (aOR 1.66; p<0.001). In hormone receptor-negative breast cancer, chemotherapy was mostly administered adjuvantly, but neoadjuvant use increased over time and was more likely in younger patients and higher T- and N-stage disease. Node-positive patients treated with NAC were less likely to have pathologically positive nodes and more likely to have less extensive axillary surgery.

Disparities in the Local Management of Breast Cancer in the US according to Health Insurance Status.

Although standard practice guidelines for breast cancer are clear, the interplay between insurance and practice patterns for the US is poorly defined. This study was performed to test for associations between patient insurance status and presentation of breast cancer as well as local therapy patterns in the US, via a large national dataset. We queried the NCI Surveillance, Epidemiology, and End Results data base for breast cancer cases diagnosed from 2007 to 2011 in women aged 18-64 with nonmetastatic ductal/lobular cancers, treated surgically. We tested for associations between insurance status (insured/Medicaid/uninsured) and choice of surgical procedure (mastectomy/breast conserving surgery [BCS]), omission of radiotherapy (RT) following BCS, and administration of post-mastectomy radiation (PMRT). There were 129,565 patients with localized breast cancer analyzed. The health insurance classification included insured (84.5%), Medicaid (11.5%), uninsured (2.1%) and unknown (1.9%). Medicaid or uninsured status was associated with large, node positive tumors, black race, and low income. The BCS rate varied by insurance status: insured (52.2%), uninsured (47.7%), and Medicaid (45.2%), p < 0.001. In multivariable analysis, Medicaid insurance remained significantly associated with receipt of mastectomy (OR [95% CI] = 1.07 [1.03-1.11]), while RT was more frequently omitted after BCS in both Medicaid (OR [95% CI] = 1.14 [1.07-1.21]) and uninsured (OR [95% CI] = 1.29 [1.14-1.47]) patients. Insurance status was associated with significant variations in breast cancer care in the US. Although patient choice cannot be determined from this dataset, departure from standard of care is associated with specific types of insurance coverage. Further investigation into the reasons for these departures is strongly suggested.

Abstract OT1-03-09: FAIRLANE: A phase II randomized, double-blind, study of the Akt inhibitor ipatasertib (Ipat, GDC-0068) in combination with paclitaxel (Pac) as neoadjuvant treatment for early stage triple-negative breast cancer (TNBC)

Abstract Background: TNBC often exhibits activation of PI3K/Akt signaling, associated with loss of PTEN expression, low INPP4B expression, and/or increased AKT3 amplification. Inhibition of the PI3K/Akt pathway in diverse cancers leads to radiosensitization and/or chemosensitization. Ipat is an oral, potent ATP-competitive small molecule inhibitor of all three isoforms of Akt. The combination of ipat with taxanes in preclinical models resulted in enhanced efficacy relative to either ipat or chemotherapy alone. In a Phase Ib clinical study, the combination of ipat with diverse chemotherapy regimens was well-tolerated and resulted in RECIST responses, particularly pts with tumors having PI3K/Akt activation. Methods: FAIRLANE is a randomized, double-blind, placebo controlled, multicenter, neoadjuvant Phase II study designed to estimate the efficacy of ipat combined with pac versus placebo combined with pac in women with Stage Ia  IIIa TNBC. Approximately 150 pts (Pts) will be enrolled, randomized in a 1:1 ratio, and stratified by PTEN status, node involvement, and tumor size. Pts will receive 3 cycles of ipat 400 mg or placebo orally once daily on Days 1 to 21 of each 28-day cycle, along with pac 80 mg/m2 every 7 days for a total of 12 doses. All pts will undergo pretreatment and Day 8 tumor tissue acquisition to evaluate pathway biomarkers. Following three cycles of treatment, pts will undergo surgery. The primary efficacy endpoint, pCR within the breast and axilla (ypT0/Tis ypN0) in all pts and in pts with PTEN low tumors, will be assessed by local pathology evaluation following completion of neoadjuvant therapy and surgery. Additional endpoints include objective response rate, safety, BCS rate, pharmacokinetics, and pathway biomarkers. Following surgical resection of primary tumor, pts are expected to continue post-operative treatment with a standard adjuvant chemotherapy regimen at physician's discretion. The study is open for accrual. Clinical trial information: NCT02301988. Citation Format: Saura C, Isakoff SJ, Calvo I, Patt D, Andersen J, Gonzalez-Martin A, Fisher J, Ciruelos E, Gil-Gil M, De la Peña L, Choi Y, Jia S, Singel S, Patel PH, Baselga J, Oliveira M. FAIRLANE: A phase II randomized, double-blind, study of the Akt inhibitor ipatasertib (Ipat, GDC-0068) in combination with paclitaxel (Pac) as neoadjuvant treatment for early stage triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-09.

Prepartum supplement level and age at weaning: I. Effects on pre- and postpartum beef cow performance and calf performance through weaning1

Objectives were to determine the interaction of prepartum supplement level and age at weaning on cow BW, BCS, milk production, reproduction, and calf performance up to weaning in a fall-calving system over 2 yr. Mature, multiparous, Angus × Simmental cows (yr 1: 326 cows, 9 pastures, BW = 632 ± 67 kg, and BCS = 5.7 ± 0.58; yr 2: 383 cows, 9 pastures, BW = 606 ± 70 kg, and BCS = 5.8 ± 0.74) were used in a split-plot design that included 3 supplement levels-no supplement (NS), low supplement (LS; 2.16 kg∙cow∙d), or high supplement (HS; 8.61 kg∙cow∙d)-and 2 ages at weaning-78 ± 11 d of age (early weaned; EW) or 186 ± 11 d of age (normal weaned; NW). Cows grazed endophyte-infected tall fescue/red clover pastures and were bunk fed supplement (70% dried distillers' grains with solubles and 30% soybean hulls) 103 ± 11 d prepartum to 2 ± 11 d postpartum. Cow BW was greater ( < 0.01) for cows fed HS at precalving (49 ± 11 d prepartum), postcalving (26 ± 11 d postpartum), and postbreeding (81 d after AI) compared with cows fed NS and LS. Prepartum supplementation did not affect ( ≥ 0.62) calf birth BW, percent of calves dead at birth, or percent of cows calving unassisted. Prepartum supplementation tended ( = 0.10) to improve AI conception. Early weaning increased ( ≤ 0.05) AI conception and postbreeding cow BW and BCS compared with cows with NW calves. Neither prepartum supplementation nor age at weaning affected ( ≥ 0.28) overall pregnancy rate. At time of early weaning, BW was increased ( = 0.05) for steers from cows fed LS compared with steers from cows fed NS. Steer BW at time of normal weaning and ADG between early and normal weaning was greater ( < 0.01) for EW steers compared with NW steers. A year × age at weaning interaction occurred ( < 0.01) for ultrasound marbling score at time of normal weaning. In yr 1, marbling was decreased ( = 0.04) for EW steers compared with NW steers; however, in yr 2, marbling was increased ( < 0.01) for EW steers compared with NW steers. In conclusion, there was no interaction between level of supplement during late gestation and age at weaning on cow BW, BCS, milk production, AI conception, and overall pregnancy rate in mature beef cows nor in their steer progeny's BW or ultrasound marbling. Both prepartum supplementation and early weaning improved cow BW, BCS, and reproduction. Minimal effects of dam prepartum supplement level on calf performance up to weaning were observed. Early weaning improved calf growth but had inconsistent effects on ultrasound marbling across years.

Abstract OT3-2-06: NEOPAL: A randomized phase II study comparing RCB response to neoadjuvant chemotherapy or letrozole-palbociclib in PAM50 defined postmenopausal luminal breast cancer

Abstract Background: HR-positive BC heterogeneously sensitive to neoadjuvant chemotherapy (NEC), with pCR rates varying from 2 to 20% at most. The alternative systemic primary therapy in ER+ breast cancer is neoadjuvant endocrine therapy (NET). Clinical response with NET is roughly 50%. It has also been suggested that NET may yield a higher rate of breast conserving surgery than NEC in ER+ disease, although pCR remains under 10% in both instances. No definite pathological criteria for response to NET has been defined so far. Within this context, the PAM 50 signature has been evaluated on numerous series of pts and has been shown to highly correlate with Residual Cancer Burden (RCB – Symmans, JCO 2007) and pCR in patients treated with NEC, as well as with the PEPI score in patients treated with NET (Ellis 2011). Palbociclib + Letrozole has been shown as a very active association as first-line metastastic treatment of HR+ Her2- BC pts on both response rates and progression free survival (Paloma-1 study). This combination could represent an interesting alternative to CT in carefully selected Luminal BC pts. Trial design and statistical methods: Open-label, randomized, parallel, multicenter, exploratory phase II study, comparing sequential standard NEC (3 FEC 100 followed by 3 Docetaxel 100) and a same duration letrozole + palbociclib combination as neoadjuvant treatment of stage II-IIIA PAM 50 defined Luminal A-Node+/Luminal B breast cancer. Medical treatment will be followed by adequate surgery and complementary chemotherapy and radiation therapy as clinically indicated. All pts will receive adjuvant chemotherapy. Randomizations are equally balanced between the 2 arms and stratified based on T2 versus T3-T4 and PAM 50 luminal A vs luminal B. A Fleming 2-step statistical design will be used in the experimental arm with an intermediate futility analysis. The target accrual is 60 pts evaluable for RCB in both arms. Eligibility criteria: Newly diagnosed pts with ER+, Her2-negative, stage II-III breast cancer will be tested for PAM50 signature. Only luminal A N+ or Luminal B (PAM50 ROR (Prosigna™) centralized evaluation) pts will be eligible and randomized. Pts must be post-menopausal women, aged &amp;gt; 18 years, bear operable unilateral invasive BC, and not be candidate or uncertain for breast conservation. Specific aims: The main objective of this trial is to evaluate the ability of each treatment strategy to provide RCB 0-I at surgery. Secondary end-points are: Clinical/radiological response rates in each treatment arm (RECIST 1.1), safety (CTC-AE V4.0), relative dose intensity of each drug in both arms, positive and negative predictive values of PAM50 ROR-defined status, assessment of several biomarkers as potential predictors of clinical and pathological response, rates of BCS, with regard to the initially planned surgery, all in both arms Target accrual: This study has started in autumn 2014. 132 pts will have to be included (estimation of 10% risk of non evaluable pts). As about 10% of PAM50 evaluable pts will be classified as non luminal, and taking into account potential technical failures, about 180 pts will be screened. Citation Format: Paul H Cottu, François Duhoux, Jérôme Lemonnier, Hervé Bonnefoi, Anne Vincent Salomon, Bernard Asselain, Suzette Delaloge. NEOPAL: A randomized phase II study comparing RCB response to neoadjuvant chemotherapy or letrozole-palbociclib in PAM50 defined postmenopausal luminal breast cancer [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 OT3-2-06.

Increasing Mastectomy Rates Among all Age Groups for Early Stage Breast Cancer: A 10-Year Study of Surgical Choice

First-line surgical options for early stage breast cancer and ductal carcinoma in situ include breast conserving surgery or mastectomy. We analyzed factors that influence the receipt of mastectomy and resultant trends over time. Registry analysis was carried out for 21,869 women who underwent up-front surgical treatment for stage 0, I or II breast cancer between 1998 and 2007 using data from the Kentucky Cancer Registry. We examined the trend of treatment over time and assessed the probability of receiving mastectomy using multivariate logistic regression. Overall, 54.5% of women received breast conservation and 45.5% received mastectomy over a 10-year period (annual BCS rate range: 46.9-61.2%). The overall mastectomy rate substantially decreased from 53.1% in 1998 to 38.8% in 2005 (p < 0.0001), but then increased to 45% in 2007 (p < 0.001). Between 2005 and 2007, the increase in mastectomies in the age groups of <50 years, 50-69 years, and ≥ 70 years was 7.5% (p = 0.0351), 4.9% (p = 0.0132) and, 8.0% (p = 0.0283), respectively. On multivariate analysis, the rate of receiving mastectomy was drastically higher for women with stage I or II (versus in situ) disease and moderate or poorly differentiated (versus well differentiated) histology. The rate was modestly higher for uninsured and government-insured (versus privately insured) patients, patients older than 70 years (versus younger), rural (versus urban) location, receptor negative (versus receptor positive) disease, and unusual histologies (versus ductal and lobular histology). There was no statistically significant difference in surgical choice with regard to race. Determinants of mastectomy for in situ and early stage breast cancer include stage, histology, age, insurance status, county of residence, receptor status. The rate of mastectomy declined until 2005 and is now increasing across all age groups, especially for women < 50 years and ≥ 70 years.

Changes in biological markers, particularly hormone receptors, due to pre-operative chemotherapy (epirubicin/docetaxel) in operable breast cancer

We investigated the correlation between biological markers prior to pre-operative chemotherapy with epirubicin and docetaxel (ET therapy) and the effect of treatment as well as the clinically significant changes in biological markers before and after chemotherapy. Since April 2002, 52 patients with tumors ≥3 cm in diameter or lymph node metastases have received pre-operative ET chemotherapy. The items investigated were ER/PgR, proliferative activity (MIB-1), etc. The correlation of changes in these factors between pre- and post-treatment status and the clinical and pathological responses was investigated. Clinical response was 82%, BCS rate was 67%. Pathological response was 31.4%. The ER/PgR positive cell rate significantly decreased from 48%/32% to 37%/14%. The MIB-1 decreased from 48% to 27%. The pathological response was significantly high in patients with low ER/PgR-positive rates and those with high MIB-1 values.

Changes in biological markers, particularly hormone receptors, due to pre-operative chemotherapy (epirubicin/docetaxel) in operable breast cancer

We investigated the correlation between biological markers prior to pre-operative chemotherapy with epirubicin and docetaxel (ET therapy) and the effect of treatment as well as the clinically significant changes in biological markers before and after chemotherapy. Since April 2002, 52 patients with tumors ≥3 cm in diameter or lymph node metastases have received pre-operative ET chemotherapy. The items investigated were ER/PgR, proliferative activity (MIB-1), etc. The correlation of changes in these factors between pre- and post-treatment status and the clinical and pathological responses was investigated. Clinical response was 82%, BCS rate was 67%. Pathological response was 31.4%. The ER/PgR positive cell rate significantly decreased from 48%/32% to 37%/14%. The MIB-1 decreased from 48% to 27%. The pathological response was significantly high in patients with low ER/PgR-positive rates and those with high MIB-1 values.

P1-11-04: Breast Cancer Treatment Resources and Guideline-Concordant Treatment in Appalachia.

Abstract Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky — a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states. Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000–2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states. Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p&amp;lt;0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia. Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-11-04.

Breast cancer treatment resources and guideline-concordant treatment in Appalachia.

216 Background: Appalachia has poorer cancer outcomes, but little research has been done regarding availability of cancer care resources in this region and how resource availability may relate to cancer outcomes. This study 1) examines associations between radiation therapy resources and receipt of radiotherapy after BCS in counties within Kentucky - a SEER state; and 2) describes spatial patterning of breast cancer treatment resources in all 13 Appalachian states. Methods: For the Kentucky analyses, county-level data from the Area Resource File and SEER registry are analyzed. Bivariate analyses and spatial lag regression using a 6-nearest neighboring counties matrix are conducted. The sample includes stage I or II primary breast cancer patients age 18+ years diagnosed in Kentucky during 2000-2007. The dependent variable is the county-level percentage of patients received BCS without radiation; independent variables include density of radiation therapy providers and facilities and other socioeconomic covariates. For the analyses of entire Appalachian region, descriptive analyses and exploratory spatial data analysis are conducted including 420 Appalachian counties and 644 non-Appalachian counties in 13 states. Results: In Kentucky 16.44% of 17,227 early stage breast cancer patients received BCS without radiation therapy (21.08% in Appalachia versus 14.80% in non-Appalachia, p&lt;0.001). Appalachian Kentucky had significantly fewer radiation oncologists and radiation therapy facilities per capita than non-Appalachian Kentucky. The number of radiation therapy facilities per capita is negatively associated with rates of BCS without radiation when controlling for covariates. Analysis of 13 Appalachian states shows that Appalachian counties, especially in the Central and Southern regions, had significant fewer physicians per capita in Surgery, Anesthesia, Clinical Pathology, and Radiation Oncology. Clustering of scarce breast cancer care resources was observed in Central Appalachia. Conclusions: Appalachian counties, especially in central Appalachia, have fewer breast cancer treatment resources than non-Appalachian counties, and resource availability is associated with cancer health disparities.

Trends in the local treatment of breast cancer: Should we be worried?

The overall rates of BCS have remained stable or slightly increased over the past decade in the United States. The CPM rates have markedly increased while unilateral mastectomy rates have decreased. Increasingly, more women are not receiving RT after BCS, particularly high-risk women. These trends have important potential untoward consequences. Strategies are being developed to ensure adequate local therapy for breast cancer patients.

Abstract MS2-1: Trends in the Local Treatment of Breast Cancer

Abstract The objective of this presentation is to evaluate recent patterns in the local treatment of breast cancer in the United States. We will concentrate on 3 specific trends: 1) mastectomy/breast-conserving surgery (BCS) rates; 2) contralateral prophylactic mastectomy (CPM) rates; and 3) use of radiation therapy (RT) after BCS. Although some single-institutional studies have reported that mastectomy rates have recently increased, a recent population-based study reported that the rates of BCS have remained stable or slightly increased over the past decade in the United States. Both single-institutional and population-based studies have reported that CPM rates have markedly increased in recent years. On the other hand, unilateral mastectomy rates have decreased. Despite the potential benefit of RT after BCS, population-based studies indicate that an increasing number of women are not receiving RT after BCS, particularly high-risk women. These trends have important potential untoward consequences, including overtreatment for some patients and undertreatment for others. Several strategies are being developed to ensure adequate local therapy for breast cancer patients. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr MS2-1.

Toward anIn VivoDissolution Methodology: A Comparison of Phosphate and Bicarbonate Buffers

The purpose of this research was to evaluate the difference between the pharmaceutical phosphate buffers and the gastrointestinal bicarbonates in dissolution of ketoprofen and indomethacin, to illustrate the dependence of buffer differential on biopharmaceutical properties of BCS II weak acids, and to recommend phosphate buffers equivalent to bicarbonates. The intrinsic dissolution rates of ketoprofen and indomethacin were experimentally measured using a rotating disk method at 37 degrees C in USP SIF/FaSSIF and various concentrations of bicarbonates. Theoretical models including an improved reaction plane model and a film model were applied to estimate the surrogate phosphate buffers equivalent to the bicarbonates. Experimental results show that the intrinsic dissolution rates of ketoprofen and indomethacin in USP and FaSSIF phosphate buffers are 1.5-3.0 times that in the 15 mM bicarbonates. Theoretical analysis demonstrates that the buffer differential is largely dependent on the drug pK(a) and second on solubility, and weakly dependent on the drug diffusivity. Further, in accordance with the drug pK(a), solubility and diffusivity, a simple phosphate surrogate was proposed to match an average bicarbonate value (15 mM) of the upper gastrointestinal region. Specifically, phosphate buffers of 13-15 mM and 3-4 mM were recommended for ketoprofen and indomethacin, respectively. For both ketoprofen and indomethacin, the intrinsic dissolution using the phosphate surrogate buffers closely approximated the 15 mM bicarbonate buffer. This work demonstrates the substantial difference between pharmaceutical phosphates and physiological bicarbonates in determining the drug intrinsic dissolution rates of BCS II weak acids, such as ketoprofen and indomethacin. Surrogate phosphates were recommended in order to closely reflect the in vivo dissolution of ketoprofen and indomethacin in gastrointestinal bicarbonates, which has significant implications for defining buffer systems for BCS II weak acids in developing in vitro bioequivalence dissolution methodology.

Changes in biological markers, particularly hormone receptors, due to pre-operative chemotherapy (epirubicin/docetaxel) in operable breast cancer

We investigated the correlation between biological markers prior to pre-operative chemotherapy with epirubicin and docetaxel (ET therapy) and the effect of treatment as well as the clinically significant changes in biological markers before and after chemotherapy. Since April 2002, 52 patients with tumors ≥3 cm in diameter or lymph node metastases have received pre-operative ET chemotherapy. The items investigated were ER/PgR, proliferative activity (MIB-1), etc. The correlation of changes in these factors between pre-and post-treatment status and the clinical and pathological responses was investigated. Clinical response was 82%, BCS rate was 67%. Pathological response was 31.4%. The ER/PgR positive cell rate significantly decreased from 48%/32% to 37%/14%. The MIB-1 decreased from 48% to 27%. The pathological response was significantly high in patients with low ER/PgR-positive rates and those with high MIB-1 values.

An evaluation of changes in biological markers (ER, PgR, or Ki67) after neoadjuvant chemotherapy (ET: epirubicin and docetaxel) in operable breast cancer

10613 Background: Neoadjuvant chemotherapy (NAC) is a valid option not only for advanced breast cancer but also for operable breast cancer. It was reported that disease-free and overall survival after NAC were equivalent to those after adjuvant therapy. The role of biological markers for the prediction of NAC may be evaluated using pathological responsiveness. In this study, we investigated the changes in biological markers such as estrogen receptor (ER), progesterone receptor (PgR), or Ki67 after NAC. Methods: Eligible patients (pts) were newly diagnosed with large primary tumors &gt; 3 cm or positive nodes. Fifty-two pts were enrolled and received epirubicin 60 mg/m2 followed by docetaxel 60 mg/m2 every 3 weeks for 4 cycles before surgery. In 51 cases out of the pts, pre-treatment needle biopsies and surgical specimen were analyzed for expression of ER, PgR, Her-2/neu, p53 and Ki67 by immunohistochemistry, and these data were compared to the pathological response. The pathological response was evaluated using the criteria of Japan Breast Cancer Society. Results: The median age was 47 (range, 29–67) and the mean tumor size was 5.2cm (range, 1.5–14.5). The clinical response was 86%; the BCS rate was 73% and pathological response was 31% including 3 cases with pCR. Regarding changes in biology after NAC, an average rate of ER positive cells significantly fell in 37% from 47% and that of PgR positive cells also fell in 14% from 32%. Most of cases, whose tumors were changed to ER/PgR negative from ER/PgR positive, were premenopausal women accompanied with amenorrhea during the treatment. Patients with lower ER, PgR, or a higher proliferation had a significantly greater benefit from NAC. The overexpression of Her2 was not correlated to pathological response, while p53 staining had a predictive value. And patients with positive nodes had a significantly favorable disease-free survival. Conclusions: The clinical effect of NAC (ET regimen) and the BCS rate by NAC were high. Although the rates of ER and PgR positive cells and proliferation were significantly reduced by NAC, a lower ER, PgR, or a higher proliferation might reflect a good pathological response. A negative change of ER or PgR by NAC might correlate with amenorrhea in premenopausal pts. No significant financial relationships to disclose.