Treatment Of Operable Breast Cancer Research Articles

Non-Surgical Definitive Treatment for Operable Breast Cancer: Current Status and Future Prospects.

This article reviews the results of various non-surgical curative treatments for operable breast cancer. Radiotherapy is considered the most important among such treatments, but conventional radiotherapy alone and concurrent chemoradiotherapy do not achieve high cure rates. As a radiosensitization strategy, intratumoral injection of hydrogen peroxide before radiation has been investigated, and high local control rates (75-97%) were reported. The authors treated 45 patients with whole-breast radiotherapy, followed by stereotactic or intensity-modulated radiotherapy boost, with or without a radiosensitization strategy employing either hydrogen peroxide injection or hyperthermia plus oral tegafur-gimeracil-oteracil potassium. Stages were 0-I in 23 patients, II in 19, and III in 3. Clinical and cosmetic outcomes were good, with 5-year overall, progression-free, and local recurrence-free survival rates of 97, 86, and 88%, respectively. Trials of carbon ion radiotherapy are ongoing, with promising interim results. Radiofrequency ablation, focused ultrasound, and other image-guided ablation treatments yielded complete ablation rates of 20-100% (mostly ≥70%), but long-term cure rates remain unclear. In these treatments, combination with radiotherapy seems necessary to treat the extensive intraductal components. Non-surgical treatment of breast cancer is evolving steadily, with radiotherapy playing a major role. In the future, proton therapy with the ultra-high-dose-rate FLASH mode is expected to further improve outcomes.

Combined modality treatment of operable breast cancer using intraoperative radiotherapy

Objective of the study: To review worldwide literature data on the efficacy of combined modality treatment including intraoperative radiation therapy (IORT) in patients with operable breast cancer (BC). Material and Мethods. Of 110 publications (2000–2021) available from Scopus, Pubmed, Elibrary and other databases, using the key “breast cancer”, “local recurrence”, “intraoperative radiotherapy” and “radiation technique”, 45 were included in the literature review. Results. Radiotherapy is of paramount importance in the organpreserving treatment of breast cancer, as numerous randomised studies have shown that the use of postoperative radiotherapy dramatically reduces the number of locoregional recurrences. The use of IORT as an effective method of relapse prevention compared to standard postoperative adjuvant radiotherapy is an important trend in radiation oncology.Conclusion. The use of IORT in combination treatment modality for operable breast cancer should be differentiated and based on clinical and morphological prognostic factors. Different molecular subtypes of breast cancer are characterized by significant differences in pathogenesis and response to therapy. Further studies on the effectiveness of IORT are required to identify a group of patients with absolute indications for the use of IORT.

Surrogacy Beyond Prognosis: The Importance of "Trial-Level" Surrogacy.

Many candidate surrogate endpoints are currently assessed using a 2-level statistical approach, which consists in checking whether (1) the potential surrogate is associated with the final endpoint in individual patients and (2) the effect of treatment on the surrogate can be used to reliably predict the effect of treatment on the final endpoint. In some situations, condition (1) is fulfilled but condition (2) is not. We use concepts of causal inference to explain this apparently paradoxical situation, illustrating this review with 2 contrasting examples in operable breast cancer: the example of pathological complete response (pCR) and that of disease-free survival (DFS). In a previous meta-analysis, pCR has been shown to be a strong and independent prognostic factor for event-free survival (EFS) and overall survival (OS) after neoadjuvant treatment of operable breast cancer. Yet, in randomized trials, the effects of experimental treatments on pCR have not translated into predictable effects on EFS or OS, making pCR an “individual-level” surrogate, but not a “trial-level” surrogate. In contrast, DFS has been shown to be an acceptable surrogate for OS at both the individual and trial levels in early, HER2-positive breast cancer. The distinction between the prognostic and predictive roles of a tentative surrogate, not always made in the literature, avoids unnecessary confusion and allows better understanding of what it takes to validate a surrogate endpoint that is truly able to replace a final endpoint.

Should oncoplastic breast conserving surgery be used for the treatment of early stage breast cancer? Using the GRADE approach for development of clinical recommendations

IntroductionThe potential advantages of oncoplastic breast conserving surgery (BCS) have not been validated in robust studies that constitute high levels of evidence, despite oncoplastic techniques being widely adopted around the globe. There is hence the need to define the precise role of oncoplastic BCS in the treatment of early breast cancer, with consensual recommendations for clinical practice. MethodsA panel of world-renowned breast specialists was convened to evaluate evidence, express personal viewpoints and establish recommendations for the use of oncoplastic BCS as primary treatment of unifocal early stage breast cancers using the GRADE approach. ResultsAccording to the results of the systematic review of literature, the panelists were asked to comment on the recommendation for use of oncoplastic BCS for treatment of operable breast cancer that is suitable for breast conserving surgery, with the GRADE approach. Based on the voting outcome, the following recommendation emerged as a consensus statement: Oncoplastic breast conserving surgery should be recommended versus standard breast conserving surgery for the treatment of operable breast cancer in adult women who are suitable candidates for breast conserving surgery (with very low certainty of evidence). DiscussionThis review has revealed a low level of evidence for most of the important outcomes in oncoplastic surgery with lack of any randomized data and absence of standard tools for evaluation of clinical outcomes and especially patients’ values.Despite areas of controversy, about one-third (36%) of panel members expressed a strong recommendation in support of oncoplastic BCS. Presumably, this reflects a synthesis of views on the relative complexity of these techniques, associated complications, impact on quality of life and costs.

Regulation of docetaxel chemosensitivity by NR2F6 in breast cancer.

Docetaxel (DTX)-based chemotherapy significantly eliminates rest cancerous cells and decreases the risk of death, thus remaining the mainstay of treatment for operable breast cancer (BCa). However, resistance or incomplete response to DTX occurs frequently, resulting in disease recurrence and poor prognosis. There is an urgent need to identify and understand the key factors and corresponding molecular bases driving this complicated pathogenesis. Herein, both data mining and profiling analysis using clinical BCa biopsies showed that expression levels of the nuclear receptor subfamily 2, group F, member 6 (NR2F6), a recently characterized central transcription factor for cancer immune surveillance, were significantly downregulated in DTX-resistant BCa. This downregulation, possibly regulated by leptin signaling, predicted a poor postoperative chemotherapy survival in DTX-resistant BCa. In both genetically engineered cell models and patient-derived xenograft models, we provided evidence that BCa cells with insufficient NR2F6 expression were less responsive to DTX treatment. Mechanistically, NR2F6 functioned as a potent corepressor of platelet-derived growth factor B receptor gene (PDGFRB) transcription by recruiting HDAC2 onto the PDGFRB promoter. Stable PDGFRB inhibition ameliorated NR2F6 deficiency-impaired response to DTX in BCa cells, indicating that NR2F6's effect on DTX response is mediated, at least in part, through transcriptional repression of PDGFRB. Collectively, our findings define NR2F6 as an negative regulator of cell survival and DTX resistance, probably by serving as a convergent point linking leptin signaling and PDGF-B/PDGFRβ axis, in BCa cells.

198P - A multicentre, international neoadjuvant (NA), randomized, double-blind phase III trial comparing fulvestrant to a combination of fulvestrant and palbociclib in patients with operable luminal breast cancer (SAFIA Trial)

BackgroundNA chemotherapy (CT) +/- anti-Her2 treatment of operable breast cancer (BC) is considered a standard option in the management of BC. However, pathologic complete response (pCR) rates with CT in HR+/Her2- BC are usually low: 7% (Luminal A) to 16% (Luminal B). Alternatively, NA endocrine therapy (ET) has not been established as a standard treatment because of low pCRs. MethodsThis is a multicenter phase III, 3rd generation NA trial performed in 34 centers and 7 countries of Middle-East and North Africa (MENA Region). The objective is to investigate the potential role of adding Palbociclib to ET (Fulvestrant +/- Goserelin) compared to ET alone as NA therapy of HR+/Her2- operable BC sensitive to ET. The primary endpoint is pCR with the hypothesis that the addition of Palbociclib would increase the pCR rate from 5% to 15%. Clinical/radiological response, conservative surgery rate, safety, disease-free and OS are secondary endpoints. Exploratory endpoints encompass biomarker serial analysis of liquid biopsies with Quantum Optic and DNA methylation technologies. ResultsA total of 400 pre and post-menopausal pts with stage II and IIIA are planned to be recruited. Oncotype DX is performed upfront in order to eliminate CT candidates. All pts with a recurrence score (RS) < 31 are treated with Fulvestrant (500mg Day (d.) 1, 14, 28 then q. 28 d. (+/- Goserelin 3.6mg q.28 d.) for 4 months. Pts with responding/stable disease are then randomized in double blind fashion to Fulvestrant (+/- Goserelin) with either Palbociclib 125mg po daily 3 weeks/4 or placebo. Four additional cycles are delivered before surgery The trial was initiated in 2018. As of April 2019, 196 patients have been enrolled. The majority of them (60%) are pre/peri menopausal. The mean age is 50.5 years (range: 25-83). RS of<31 was reported in 75% of cases. So far, 96 pts have completed the induction ET and were randomized to ET with or without Palbociclib. End of accrual is expected by end of 2019. ConclusionsSAFIA trial aims to evaluate whether or not the addition of a CDK 4/6 inhibitor to pts sensitive to ET would validate a neo-adjuvant strategy without CT in luminal operable BC. Clinical trial identificationNCT03447132. Legal entity responsible for the studyInternational Cancer Research Group (ICRG). FundingPfizer, AstraZeneca and Genomic Health. DisclosureAll authors have declared no conflicts of interest.

Abstract P6-02-09: Diagnostic performance of dedicated breast PET for the prediction of pathological response after neoadjuvant chemotherapy

Abstract Background: Neoadjuvant chemotherapy (NAC) is a standard treatment for operable breast cancer. However, imaging methods for evaluating treatment response have not been established. Previous studies reported that ring-type dedicated breast positron emission tomography (DbPET) detected residual tumors following NAC more accurately than whole-body PET/CT. This study assessed DbPET parameters for predicting pathological complete response (pCR) in patients with breast cancer. Patients and Methods: Among patients with breast cancer who underwent surgery after NAC, 61 were examined using ring-type DbPET before and after NAC. The maximum standardized uptake values (SUVmax) and tumor-to-normal-tissue ratio (TNR) were calculated before and after NAC (pre-SUVmax, pre-TNR, post-SUVmax and post-TNR, respectively). Moreover, the reduction rates (ΔSUVmax and ΔTNR) were determined. pCR was defined as complete remission of breast cancer. Results: The median patient age was 52 years. Forty patients (65.6%) were estrogen receptor (ER)-positive, whereas 25 patients (41.0%) were HER2-positive. Fifteen patients (24.6%) achieved pCR after NAC. The calculated values for the parameters of DbPET are summarized in Table 1. The most promising parameters for predicting pCR were ΔSUVmax (area under the curve [AUC]: 0.506) and post-TNR (AUC: 0.640). Although neither of these two parameters reflected the pathological response to NAC in patients with ER-positive disease, post-TNR showed the highest AUC (i.e., AUC: 0.750) for pCR in patients with ER-negative disease. The sensitivity and specificity of post-TNR in the ER-positive group were 85.7% and 39.4%, respectively. In the ER-negative group, these values were 100% and 58.3%, respectively [Table 2] Table 1.Diagnostic performance of dedicated breast positron-emission tomography for the prediction of pathological complete response after neoadjuvant chemotherapyParameterspCR Median (IQR)Non-pCR Median (IQR)PAUC (95% CI)Pre-SUVmax14.8 (9.2–17.7)14.4 (10.7–19.8)0.6040.454 (0.285–0.624)Post-SUVmax1.8(1.5–2.1)2.0 (1.6–3.4)0.2370.603 (0.460–0.746)ΔSUVmax (%)87.32 (81.5–91.8)88.6(82.8–91.8)0.9540.506 (0.329–0.682)Pre-TNR8.0 (5.3–9.2)7.3(5.9–10.2)0.7570.472 (0.297–0.647)Post-TNR1.7(1.0–1.1)1.2 (1.0–2.4)0.0980.640 (0.506–0.774)ΔTNR (%)87.3 (78.3–89.1)79.8 (62.7–86.7)0.1130.638 (0.472–0.803)pCR, pathological complete response; IQR, interquartile range; AUC, area under the curve; CI, confidence interval, SUV, standardized uptake value; TNR, tumor-to-normal-tissue ratio.Table 2.Diagnostic accuracy of post-TNR according to estrogen receptor status Sensitivity (%)Specificity (%)Accuracy (%)PPV (%)NPV (%)ER-positive85.739.447.523.192.9ER-negative10058.375.061.5100TNR, tumor-to-normal-tissue ratio; ER, estrogen receptor; PPV, positive predictive value; NPV, negative predictive value Conclusion: In DbPET, ΔSUVmax and post-TNR were shown to be promising parameters for predicting pathological response to NAC. Post-TNR provided the highest sensitivity for predicting pCR in patients with ER-negative breast cancer. Citation Format: Suzuki E, Sasada S, Sueoka S, Masumoto N, Goda N, Kajitani K, Emi A, Haruta R, Kadoya T, Kataoka T, Okada M. Diagnostic performance of dedicated breast PET for the prediction of pathological response after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-02-09.

Institutional variation in surgical care for early-stage breast cancer at community hospitals

BackgroundThere is significant institutional variation in the surgical care of breast cancer, and this may reflect access to services and resultant physician practice patterns. In previous studies, specialty care has been associated with variation in the operative treatment of breast cancer but has not been evaluated in a community setting. This study investigates these issues in a cohort of 59 community hospitals in the United States. Materials and methodsData on patients receiving an operation for breast cancer (2006-2009) in a large, geographically diverse cohort of hospitals were obtained. Administrative data, autoabstracted cancer-specific variables from free text, and multiple other data sets were combined. Polymotous logistic regression with multilevel outcomes identified associations between these variables and surgical treatment. ResultsAt 59 community hospitals, 4766 patients underwent breast conserving surgery (BCS), mastectomy, or mastectomy with reconstruction. The older patients were most likely to receive mastectomy alone, whereas the younger age group underwent more reconstruction (age <50), and BCS was most likely in patients aged 50-65. Surgical procedure also varied according to tumor characteristics. BCS was more likely at smaller hospitals, those with ambulatory surgery centers, and those located in nonmetropolitan areas. The likelihood of reconstruction doubled when there were more reconstructive surgeons in the health services area (P = 0.02). BCS was more likely when radiation oncology services were available within the hospital or network (P = 0.04). ConclusionsInterpretation of these results for practice redesign is not straightforward. Although access to specialty care is statistically associated with type of breast surgical procedure, clinical impact is limited. It may be more effective to target other aspects of care to ensure each patient receives treatment consistent with her individual preferences.

Factors that predict recurrence later than 5years after initial treatment in operable breast cancer.

BackgroundOccasionally, breast cancer relapses more than 5 years after initial treatment, sometimes with highly aggressive disease in such late-recurring patients. This study investigated predictors of recurrence after more than 5 years in operable breast cancer.MethodsWe retrospectively analyzed data from patients with recurrent breast cancer treated at Siriraj Hospital. Patients were divided into those whose relapse times were longer or shorter than 5 years. Factors that predicted late recurrence were analyzed in both the overall population and the luminal subgroup. Patterns of relapse, changes in biomarkers, and time to disease progression after first relapse were also recorded.ResultsWe included 300 women whose breast cancers recurred between 2005 and 2013, of whom 180 had recurrence within 5 years of diagnosis and 120 later than 5 years (median time to recurrence: 45.43 months; range: 4.4–250.3 months). Tumors larger than 2 cm, lymph node metastasis, and high nuclear grade were related with early recurrence. Estrogen receptor-positive, progesterone receptor-positive, and HER2− disease predicted late recurrence. Almost all late-relapsing patients with luminal tumors had high estrogen receptor (ER+) titers (≥50 %) and HER2− disease. Liver and brain were the most common early recurrence sites. Biomarkers did not significantly change by time of recurrence.ConclusionsER+/PR+ and HER2− patients have higher risk of recurrence later than 5 years, especially in patients with high ER titer and low nuclear grade. Larger and node-positive tumors had higher risk of early recurrence.

Omission of axillary dissection after a positive sentinel lymph-node: Implications in the multidisciplinary treatment of operable breast cancer.

Omission of axillary dissection in women with breast cancer and one or two positive sentinel-node biopsy is a major advancement in the management of this disease. Supported by a sound rationale and confirmed by prospective, randomized trials, omission of axillary dissection is now recommended in women who have undergone breast conserving surgery and who are candidate to adjuvant radiotherapy. Because breast cancer is best managed in the context of a multidisciplinary team, this surgical shift in the paradigm is expected to have implications that extend also to the other specialties involved in the team. In fact, the full evaluation of the axillary tumor burden has been historically considered an essential part of tumor staging and the absolute number of involved node critical information to tailor post-surgical treatments. Lack of this information in a patient with axillary involvement documented by a positive sentinel lymph-node biopsy may represent a challenge when deciding on further, post-surgical treatments. This review will address the critical aspects and the potential implications of omission of axillary dissection in the context of the multidisciplinary breast team.

A phase II trial of dose-dense (biweekly) paclitaxel plus carboplatin as neoadjuvant chemotherapy for operable breast cancer

The aim of the present study is to investigate the efficacy and safety of dose-dense (biweekly) carboplatin and paclitaxel as a neoadjuvant treatment for operable breast cancer. Patients with previously untreated breast cancer (stages Ic-III) were treated with four cycles of paclitaxel (175 mg/m(2), intravenous drip, D1) and carboplatin (area under the curve of 5, D1). Patients with HER2+ disease simultaneously received trastuzumab (6 mg/kg initial dose with subsequent doses of 4 mg/kg biweekly). The primary endpoint was a pathologically complete response (pCR). Between January 2012 and February 2014, 110 patients were enrolled. The overall pCR rate was 35.45 % (39 of 110). The pCR rates for the different cancer subtypes were as follows: 10.53 % (2 of 19) among the patients with the luminal A subtype, 12.50 % (5 of 40) among the patients with the luminal B (HER2-) subtype, 58.33 % (14 of 24) among the patients with the luminal B (HER2+) subtype, 57.14 % (8 of 14) among the patients with the triple-negative subtype, and 76.92 % (10 of 13) among the patients with the HER2+ subtype. The patients experienced the following toxicity side effects: grade 3/4 neutropenia (N = 27, 24.55 %), grade 3/4 anemia (N = 6, 5.45 %), grade 3/4 thrombocytopenia (N = 2, 1.82 %), grade 3 alanine aminotransferase (ALT) elevation (N = 1, 0.91 %), grade 3 neuropathy (N = 3, 2.73 %), grade 3 pain (N = 2, 1.82 %), and grade 3 fatigue (N = 1, 0.91 %). In total, 19.09 % of the patients experienced treatment delay or discontinuation due to hematological toxicity, and one patient discontinued treatment due to non-hematological toxicity. Neoadjuvant biweekly paclitaxel plus carboplatin is a feasible therapy that achieved high pCR rates in patients with the HER2+, triple-negative, and luminal B (HER2+) cancer subtypes (NCT0205986).

Conservative surgery and radiation therapy in the treatment of operable breast cancer.

Conservative surgery and radiation therapy in the treatment of operable breast cancer.

Utility of neoadjuvant chemotherapy in the treatment of operable breast cancer.

Neoadjuvant chemotherapy (NAC) is a legitimate alternative to first-line surgical therapy for the treatment of breast cancer patients, as level one evidence shows the effect on overall survival is equivalent to that of adjuvant chemotherapy. In the treatment of women with operable breast cancer, NAC provides a number of potential advantages including: improving the chance of achieving breast-conserving surgery, improving cosmesis after breast-conserving surgery, downstaging the breast and axilla, allowing time to fully consider surgical options, time for genetic testing and facilitating breast reconstruction in otherwise high-risk patients. However, in Australia, NAC is poorly utilized with less than 3% of women with operable breast cancer receiving NAC. This review discusses the potential harms and benefits of NAC, discusses areas of controversy in the use of NAC and describes how we have used NAC in our own practice. We conclude that if it is obviously necessary for the newly presenting breast cancer patient to have chemotherapy as part of the treatment, it is worth considering NAC. In many patients, the potential benefits of NAC outweigh the harms. However, maximizing these benefits is closely aligned with appropriate patient selection and timely multidisciplinary team communication.

Abstract 1083: Host-tumor immune response for early breast cancer patients treated with radiofrequency ablation therapy

Abstract [Background] We demonstrated immune suppression of regulatory T (Treg) cells in preoperative breast cancer (BC) patients at AACR 2011. Last year we also reported at this meeting that Th17 cells might have some potential to control tumor progression in the same cohort. Modern treatment of operable BC consists of breast surgery, drug therapy and radiation therapy. [Aim] To explore new strategy of BC treatment, we conducted a phase II study on radiofrequency ablation (RFA) in early BC between 2009 and 2013. Twenty patients were enrolled. To examine host-tumor immune response under thermal ablation therapy, Treg cells in peripheral blood mononuclear cells (PBMC) and plasma IL-17A were measured. [Patients and methods] Blood samples were collected from 13 patients before RFA and at the time of 1 month after RFA. Treg cells were examined by counting CD4+CD25highCD127low/-cells in PBMC. Plasma IL-17A was measured using cytometric beads array system. Statistical significance was analyzed using Mann-Whitney U-test. [Results] As of November 2013, all patients were free of recurrence. The percentages of Treg cells had no significant change in 13 patients before and after RFA (2.8% versus 2.7% of CD4-positive cells at mean value). In addition, there was no statistical difference in levels of plasma IL-17A before and after RFA (76 pg/ml versus 116 pg/ml at mean level). [Discussion] Unexpectedly, RFA had no favorable immune response in BC patients, because we observed significant decrease in percentages of Treg cells after breast surgery. The reason is that most patients had T1 tumor and Luminal A-like BC. They had lower percentages of Treg cells in comparison to those of tumor-bearing patients reported previously (2.8% versus 4.2%). [Conclusion] RFA is a promising alternative to breast surgery. However, it may make little effect on host-tumor immune response in favorable subtype of early BC. Citation Format: Shigeru Imoto, Noriko Nakatsugawa, Takayuki Ueno, Hiroki Ito, Kentaro Imi, Kaisuke Miyamoto, Manami Kitamura, Hirotsugu Isaka, Tetsuya Nakatsura. Host-tumor immune response for early breast cancer patients treated with radiofrequency ablation therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1083. doi:10.1158/1538-7445.AM2014-1083

A phase II neoadjuvant trial of sequential triweekly nanoparticle albumin-bound paclitaxel and cyclophosphamide followed by 5-fluorouracil/epirubicin/ cyclophosphamide in the treatment of operable breast cancer.

1066 Background: Nanoparticle albumin-bound (nab) Paclitaxel has shown favorable efficacy and toxicity profiles compared to other taxanes in the treatment of metastatic breast cancer. In this phase II trial, we evaluated a nab-paclitaxel-containing neoadjuvant regimen in patients with operable breast cancer. Methods: Fifty-five women with operable breast cancer without prior treatment were enrolled. All patients were to receive tri-weekly nab-paclitaxel and cyclophsphamide (TRI-ABC) followed by 5-fluorouracil/epirubicin/cyclophosphamide (FEC) every 3 weeks for 4 cycles. Tri-weekly trastuzumab was administered concomitant with TRI-ABC in HER2-positive (HER2+ or 3+) patients. Primary endpoint was pathologic complete response (pCR; CR) rate in breast cancer tissue and lymph nodes. Secondary endpoints included clinical response, safety, rate of breast conserving surgery and disease-free survival. Results: Fifty-four patients received at least 1 dose of chemotherapy and were included in this analysis. All pati...

Surgery versus primary endocrine therapy for operable primary breast cancer in elderly women (70 years plus).

Several studies have evaluated the clinical effectiveness of endocrine therapy alone in women aged 70 years or over with operable breast cancer and who are fit for surgery. To systematically review the evidence for the clinical effectiveness of surgery (with or without adjuvant endocrine therapy) in comparison to primary endocrine therapy in the treatment of operable breast cancer in women aged 70 years and over, both in terms of local progression and mortality. We conducted an updated search of the Cochrane Breast Cancer Group's Specialised Register (27th March 2013) and new searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 3), MEDLINE, EMBASE, the World Health Organization's International Clinical Trials Registry Platform (apps.who.int/trialsearch/) and www. gov, using the search terms 'early breast cancer', 'endocrine therapy', 'psychosocial' or 'surgery'. Randomised trials comparing surgery, with or without adjuvant endocrine therapy, to primary endocrine therapy in the management of women aged 70 years or over with early breast cancer and who were fit for surgery. We assessed studies for eligibility and quality, and two review authors independently extracted data from published trials. We derived hazard ratios for time-to-event outcomes, where possible, and used a fixed-effect model for meta-analysis. We extracted toxicity and quality-of-life data, where present. Where outcome data were not available, we contacted trialists and requested unpublished data. We identified seven eligible trials, of which six had published time-to-event data and one was published only in abstract form with no usable data. The quality of the allocation concealment was adequate in three studies and unclear in the remainder. In each case the endocrine therapy used was tamoxifen. Data, based on an estimated 1081 deaths in 1571 women, did not show a statistically significant difference in favour of either surgery or primary endocrine therapy in respect of overall survival. However, there was a statistically significant difference in terms of progression-free survival, which favoured surgery with (474 participants) or without endocrine therapy (164 participants). The hazard ratios (HRs) for overall survival were: HR 0.98 (95% confidence interval (CI) 0.81 to 1.20, P = 0.85; 3 trials, 495 participants) for surgery alone versus primary endocrine therapy; HR 0.86 (95% CI 0.73 to 1.00, P = 0.06; 3 trials, 1076 participants) for surgery plus endocrine therapy versus primary endocrine therapy. The HRs for progression-free survival were: HR 0.55 (95% CI 0.39 to 0.77, P = 0.0006) for surgery alone versus primary endocrine therapy; HR 0.65 (95% CI 0.53 to 0.81, P = 0.0001) for surgery plus endocrine therapy versus primary endocrine therapy (each comparison based on only one trial). Tamoxifen-related adverse effects included hot flushes, skin rash, vaginal discharge, indigestion, breast pain, sleepiness, headache, vertigo, itching, hair loss, cystitis, acute thrombophlebitis, nausea, and indigestion. Surgery-related adverse effects included paraesthesia on the ipsilateral arm and lateral thoracic wall in those who had axillary clearance. One study suggested that those undergoing surgery suffered more psychosocial morbidity at three months post-surgery, although this difference had disappeared by two years. Primary endocrine therapy should only be offered to women with oestrogen receptor (ER)-positive tumours who are unfit for surgery, at increased risk of serious surgical or anaesthetic complications if subjected to surgery, or who refuse surgery. In a cohort of women with significant co-morbid disease and ER-positive tumours it is possible that primary endocrine therapy may be a superior option to surgery. Trials are needed to evaluate the clinical effectiveness of aromatase inhibitors as primary therapy for an infirm older population with ER-positive tumours.

Readability of online patient resources for the operative treatment of breast cancer

Increasing use of Internet resources for health information is important in promoting patient involvement in medical care and decision-making. The National Institutes of Health and American Medical Association have recommended that patient health information should be written at a sixth-grade reading level. This study evaluates the readability of the most commonly used Internet resources for the operative treatment of breast cancer in the context of average American literacy. The top 10 websites for "breast cancer surgery" based on public Internet search engines were identified. Patient-directed content was downloaded from all relevant articles on these sites. A total of 104 articles were assessed with the use of 10 established readability analyses. Average readability scores were analyzed for all articles as well as by website. The overall average reading level across all sites was 12.9; this was similar between tests (Coleman-Liau 12.6, Flesch Kincaid 12.3, FORCAST 11.2, Fry 14, Gunning Fog 14.4, New Dale-Chall 12.4, New Fog 11, Raygor 14, and Simple Measure of Gobbledygook 14.3). Comparing readability by website showed disparity in average reading level from 11.2 to 16.5. Online patient resources for breast cancer surgery exceed recommended reading levels and are too difficult to be understood by a large portion of the United States population.

Abstract P3-12-13: First analysis of ASTER study AT for 3 cycles followed by CMF for 3 cycles as neo or adjuvant chemotherapy in early stage breast cancer. A single institution experience

Abstract Background: The ECTO study demonstrated the efficacy of concurrent doxorubicin and paclitaxel (AT) for 4 cycles followed by cyclophosphamyde/ methotrexate/fluorouracil (CMF) for 4 cycles in the neoadjuvant and adjuvant treatment of operable breast cancer (Gianni L. et al. JCO 2009). With the purpose of ameliorating the tolerability of the regimen, we designed the ASTER study to reduce both the duration and the total dose of treatment with AT followed by CMF. Herein we report on the first data of efficacy of the study and the toxicity. Methods: A total of 345 patients with operable breast cancer were enrolled between September 2008 and November 2011. Median age was 50 years (range 23-74); 74.5% of patients presented with hormonal receptor positive (HR +) and 23,5% of patients with both hormonal receptor negative (HR-PgR-); 19% of patients presented HER2 over expression/amplification; half patients had Ki67 &amp;gt;14%, almost of patients had pT1 (66%) or pT2 (30%) with 27,5% of pN0. Patients were treated with Adriamycin (60 mg/mq) + Paclitaxel (200 mg/mq) q21 for 3 cycles followed by CMF i.v. 1, 8q28 for 3 cycles (73 as neo-adjuvant and 272 as adjuvant regimen). After chemotherapy in patients with HER2+ trastuzumab was delivered for 1 yr and in patients with HR+ tumors hormonal treatment was recommended for 5 yr. Breast irradiation was mandatory after conserving surgery (64% of cases). Results: At a median follow-up of 36 months, the relapse free survival (RFS) and overall survival (OS) were 92% and 96% respectively. As expected in patients HR+/HER2- RFS were 95% and OS 99%, in patients HER2+ RFS were 90% and OS 97% and in those HR-/HER2- 83% and 79% respectively. In the neoadjuvant subset tnpCR, defined as the absence of invasive cells in the primary tumor and in nodes, was obtained in 10% of cases. A tnpCR was achieved in 27% of patients with triple negative cancer and only in 5% of HR positive cancer. Peripheral neuropathy toxicity was reported in 37% of cases and was essentially mild to moderate. Only 8,7% of patients experienced neutropenia G 3, 4,3% GI toxicity G3 and 2,3% mucositis G3. No cardiotoxicity was documented even in the 65 patients who received postoperative trastuzumab to date. Conclusions: This results of Aster study AT for 3 cycles followed by CMF for 3 cycles showed similar efficacy and very favorable toxicity compared whit our previous experience of eighth cycle of sequential and non cross resistant chemotherapy in early stage breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P3-12-13.

Magnetic resonance imaging as a predictor of pathologic response in patients treated with neoadjuvant systemic treatment for operable breast cancer

Increased pathologic complete response (pCR) rates observed with neoadjuvant chemotherapy (NCT) for some subsets of patients with invasive breast cancer have prompted interest in whether patients who achieved a pCR can be identified preoperatively and potentially spared the morbidity of surgery. The objective of this multicenter, retrospective study was to estimate the accuracy of preoperative magnetic resonance imaging (MRI) in predicting a pCR in the breast. MRI studies at baseline and after the completion of NCT plus data regarding pathologic response were collected retrospectively from 746 women who received treatment at 8 institutions between 2002 and 2011. Tumors were characterized by immunohistochemical phenotype into 4 categories based on receptor expression: hormone (estrogen and progesterone) receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 327), HR-positive/HER2-positive, (n = 148), HR-negative/HER2-positive, (n = 101), and triple-negative (HR-negative/HER2 negative; n = 155). In all, 194 of 249 patients (78%) with HER2-positive tumors received trastuzumab. Univariate and multivariate analyses of factors associated with radiographic complete response (rCR) and pCR were performed. For the total group, the rCR and pCR rates were 182 of 746 patients (24%) and 179 of 746 patients (24%), respectively, and the highest pCR rate was observed for the triple-negative subtype (57 of 155 patients; 37%) and the HER2-positive subtype (38 of 101 patients; 38%). The overall accuracy of MRI for predicting pCR was 74%. The variables sensitivity, negative predictive value, positive predictive value, and accuracy differed significantly among tumor subtypes, and the greatest negative predictive value was observed in the triple-negative (60%) and HER2-positive (62%) subtypes. The overall accuracy of MRI for predicting pCR in invasive breast cancer patients who were receiving NCT was 74%. The performance of MRI differed between subtypes, possibly influenced by differences in pCR rates between groups. Future studies will determine whether MRI in combination with directed core biopsy improves the predictive value of MRI for pathologic response.

Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated with Neoadjuvant Systemic Treatment for Operable Breast Cancer (TBCRC 017)

Magnetic Resonance Imaging as a Predictor of Pathologic Response in Patients Treated with Neoadjuvant Systemic Treatment for Operable Breast Cancer (TBCRC 017)