Early Operable Breast Cancer Research Articles

Prevalence of Distant Metastases in High-Risk Operable Breast Cancer (HROBC) pT1-2 N2a or Higher at Diagnosis

AbstractCurrent standard guidelines do not recommend a routine staging workup in early operable breast cancer (OBC) as the incidence of de novo metastasis is only 1–2%. Some of these patients are at high risk for relapse based on the higher axillary nodal burden. This prospective study evaluated the presence of de novo asymptomatic distant metastases in HROBC with pT1/2 N2a/N3 on upfront surgery. A single-centre study was carried out in upfront operated OBC patients with four or more axillary nodes positive after definitive surgery. Comprehensive metastatic workup was carried out, including an ultrasound abdomen, bone scan, and CT scan (thorax-abdomen-pelvis) or PET scan before initiating adjuvant treatment. If a distant disease was detected, the adjuvant treatment intent was tailored accordingly. The study accrued a prospective consecutive cohort of 97 women with pT1-2 N2a-3 during 2015–2018 operated upfront for OBC with cT1-2 N0-1. Forty percent of women were premenopausal, 54 (55.6%) had pN2a, and 43 (44.3%) had pN3 disease. Distant disease was seen in 8 of 97 women (8.24%) of these high-risk early cancers, 5 had oligometastatic denovo disease (5.15%), and 3 had polymetastatic (3.09%). Between the 2 groups, the pickup rate of distant disease was higher in pN3 (11.4%) as against pN2a (5.6%), p = NS. Only 3.09% of patients with extensive metastases were treated with palliative intent. The study shows potential to optimize the management of HROBC with heavy nodal disease identified post-primary surgery by selective staging investigations, adequate resource stratification, and thereby improved management, including modifying treatment plans early.

Postoperative radiotherapy in women with early operable breast cancer (Scottish Breast Conservation Trial): 30-year update of a randomised, controlled, phase 3 trial

Breast-conserving surgery, adjuvant systemic therapy, and radiotherapy are the standard of care for most women with early breast cancer. There are few reports of clinical outcomes beyond the first decade of follow-up of randomised trials comparing breast-conserving surgery with or without radiotherapy. We present a 30-year update of the Scottish Breast Conservation Trial. In this randomised, controlled, phase 3 trial across 14 hospitals in Scotland, women aged younger than 70 years with early breast cancer (tumours ≤4 cm [T1 or T2 and N0 or N1]) were included. They underwent breast-conserving surgery (1 cm margin) with axillary node sampling or clearance. Oestrogen receptor (ER)-rich patients (≥20 fmol/mg protein) received 20 mg oral tamoxifen daily for 5 years. ER-poor patients (<20 fmol/mg protein) received chemotherapy (cyclophosphamide 600 mg/m2, methotrexate 50 mg/m2, and fluorouracil 600 mg/m2 every 21 days intravenously in eight courses). Stratification was by menstrual status (within or more than 12 months from last menstrual period) and ER status (oestrogen concentration ≥20 fmol/mg protein, <20 fmol/mg protein, or unknown) and patients were randomly assigned (1:1) to high-dose (50 Gy in 20-25 fractions) local or locoregional radiotherapy versus no radiotherapy. No blinding was possible due to the nature of the treatment. We report the primary endpoint of the original trial, ipsilateral breast tumour recurrence, and the co-primary endpoint, overall survival. Clinical outcomes were compared by the log-rank test. Hazard ratios (HRs) are reported, with no radiotherapy as the reference group. Failures of the proportional hazards assumption are reported if significant. All analyses are by intention to treat. Between April 1, 1985, and Oct 2, 1991, 589 patients were enrolled and randomly assigned to the two treatment groups (293 to radiotherapy and 296 to no radiotherapy). After exclusion of four ineligible patients (two in each group), there were 291 patients in the radiotherapy group and 294 patients in the no radiotherapy group. Median follow-up was 17·5 years (IQR 8·4-27·9). Ipsilateral breast tumour recurrence was significantly lower in the radiotherapy group than in the no radiotherapy group (46 [16%] of 291 vs 107 [36%] of 294; HR 0·39 [95% CI 0·28-0·55], p<0·0001). Although there were differences in the hazard rate for ipsilateral breast tumour recurrence in the first decade after treatment (HR 0·24 [95% CI 0·15-0·38], p<0·0001), subsequent risks of ipsilateral breast tumour recurrence were similar in both groups (0·98 [0·54-1·79], p=0·95). There was no difference in overall survival between the two groups (median 18·7 years [95% CI 16·5-21·5] in the no radiotherapy group vs 19·2 years [16·9-21·3] in the radiotherapy group; HR 1·08 [95% CI 0·89-1 ·30], log-rank p=0·43). Our findings suggest that patients whose biology predicts a late relapse a decade or more after breast-conserving surgery for early breast cancer might gain little from adjuvant radiotherapy. Breast Cancer Institute (part of Edinburgh and Lothian Health Foundation) and PFS Genomics (now part of Exact Sciences).

Efficacy and safety of neoadjuvant trastuzumab, pyrotinib, and dalpiciclib without chemotherapy in early-stage HR-negative/HER2-positive breast cancer: An open-label, single-arm phase II trial.

e12613 Background: The chemotherapy-free neoadjuvant regimens of dual HER2 blockade has showed encouraging rates of pathological complete response (pCR) in patients with HER2-positive breast cancer. Additionally, combining cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors with anti-HER2 therapy has shown synergistic effects in hormone receptor (HR)-positive and HER2-positive breast cancer. However, there is limited data regarding this combination strategy in HR-negative/HER2-positive settings. The objective of this study was to evaluate the efficacy and safety of a chemotherapy-free regimen consisting of the CDK4/6 inhibitor dalpiciclib, and dual anti-HER2 components of pyrotinib and trastuzumab in patients with HR-negative/HER2-positive early breast cancer (EBC). Methods: This open-label, single-arm, phase II study was designed using the Simon two-stage method (Registration number: Chi-CTR-2200060748). Patients with HR-negative/HER2-positive operable EBC (tumor stage T1-3 and nodal stage N0-2) were enrolled. Eligible patients received trastuzumab (HLX02, 8 mg/kg loading dose, followed by 6 mg/kg every 3 weeks intravenously) for 15 weeks, plus pyrotinib (240 mg daily orally) and dalpiciclib (125 mg daily orally for 3 weeks, followed by 1 week off) for 16 weeks. Surgery was performed 3-6 weeks after the completion of the last cycle of study treatment. The primary endpoint was pCR (ypT0/Tis ypN0) at surgery, and secondary endpoints included objective response rate (ORR), change of Ki-67 labeling index, biomarker analysis, survival and safety. Results: Between Jun 24, 2022, and Sept 14, 2023, a total of 30 patients with a median age of 54.5 years (range: 35-66) were enrolled and treated in this ongoing trial. As of the data cutoff date on Jan 20, 2024, 26 patients underwent surgery, and pCR was achieved in 18 (69.2%) cases. Out of the 29 patients with evaluable response, 26 achieved partial response and 3 achieved stable disease, resulting in an ORR of 89.7%. The most common grade 3 or more treatment-related adverse events (AEs) were diarrhea (66.7%), decreased neutrophil count (33.3%), and decreased white blood cell count (20.8%). Most AEs were tolerable, and no treatment-related deaths occur. Conclusions: In patients with HR-negative/HER2-positive EBC, a dual HER2-targeted combination of pyrotinib and trastuzumab, along with dalpiciclib in the absence of chemotherapy showed promising efficacy with encouraging pCR and ORR rates, as well as a favorable safety profile in the neoadjuvant setting. Clinical trial information: Chi-CTR-2200060748.

Perspectives and possibilities of preserving reproductive function in patients receiving antitumor treatment. Clinical observation

Currently, treatment of patients with early primary operable BRCA mutation-associated breast cancer requires integrative approach. A mutation in BRCA1/2 genes is a prognostically unfavorable factor increasing the risk of cancer of the contralateral breast, as well as ovaries, pancreas, fallopian tubes, and primary peritoneal cancer. In this clinical observation, an integrative multidisciplinary approach to treatment of a young patient with luminal B breast cancer is described which allowed to preserve the patient’s fertility and achieve pregnancy using assisted reproductive technologies.High effectiveness of the chosen treatment tactics in the framework of integrative approach in a specialized medical facility with experience in treatment of oncological diseases and preservation of reproductive function confirmed by clinical data and results of laboratory and instrumental exams is demonstrated.

Evaluation of Dual Dye Technique for Sentinel Lymph Node Biopsy in Breast Cancer: Two-Arm Open-Label Parallel Design Non-Inferiority Randomized Controlled Trial.

Radioisotope and blue dye are standard agents for performing sentinel lymph node (SLN) biopsy in breast cancer. The paucity of nuclear medicine facility poses logistic challenge. This study evaluated performance of radioisotope & methylene blue (MB) with indocyanine green (ICG) and MB for SLNB. This randomized controlled trial was conducted from December 2019 to July 2022 comparing SLN identification proportions of radioisotope-blue dye [Group A] with dual dye (MB + ICG; Group B]. Secondary objective included time required and cost effectiveness of performing SLNB. Sample size of 70 (35 in each arm) was calculated. Upfront operable node negative early breast cancer was included in the study. Clinico-demographic data, number & type of SLN, time taken were noted. Cost analysis was done including the equipment, manpower & consumables. Chi-square/Fisher exact test was used to compare proportion between two groups. p value of less than 0.05 was considered to represent statistical significance. Seventy patients randomized to either group were similar in clinico-demographic and tumor characteristics. SLN identification rate (IR) was 91.43% in group A and 100% in group B. Overall IR of MB, radioisotope and ICG were 91.43%, 91.43% and 100%, respectively. Mean number of SLNs identified were 3 in group A and 4 in group B. Median time required for SLNB was 12min and 14min in either group, respectively. Cost of performing SLNB was higher in Group B. SLNB using dual dye is non-inferior to radioisotope-blue dye in upfront operable early breast cancer. Trial registration number Clinical Trial registry India CTRI/2020/02/023503.

The Oncotype DX Recurrence Score's Impact on the Management of Oestrogen-Positive/Human Epidermal Growth Factor Receptor 2-Negative, Low-Burden Axillary Status Breast Cancer (REHAB Study): Results of a Single Centre.

BackgroundThe Oncotype DX Recurrence Score (ODX-RS) is increasingly utilized in oestrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative, low-burden axillary disease early operable breast cancer. It has been demonstrated to predict the benefits of adjuvant chemotherapy, hence supporting individualized decisions on adjuvant therapy.AimTo investigate the application of ODX-RS as an adjuvant treatment decision tool in breast cancer operated in our unit.MethodsA total of 107 eligible patients who were operated on between 2017 and 2021 in Basildon University Hospital, UK were enrolled in this study. In this retrospective study, the clinical data, including patient’s age, tumour size, ER status, HER2 status, Ki67 proliferative index (Ki67-PI), nodal status, tumour grade, and ODX-RS, were collected. In the study design, the oncologist had the opportunity to assess the need for adjuvant chemotherapy for patients with ER-positive, HER2-negative, low-burden axillary lymph node disease, early breast cancer by using tumour characteristics and the PREDICT tool without knowing the ODX-RS results. The clinician's decision was matched against the breast multidisciplinary team's recommendations after ODX-RS utilisation, and the results were explored.ResultsThe median ODX-RS of cohort tumours was 18 in the age group > 50 years, with ODX-RS ≥ 26 found in 18% of the group (n = 12). In the age group ≤ 50 years, 17% (n = 7) had ODX-RS between 21 and 25 and only 7% (n = 3) had ODX-RS ≥ 26. Without using ODX-RS, only 16% of the patients had been offered adjuvant chemotherapy in addition to the hormonal manipulation therapy; however, after using ODX-RS, up to 33% of the cohort was suitable for adjuvant chemotherapy in addition to the hormonal manipulation therapy. The changes in the recommendations after ODX-RS utilisation have been noticed in 29% of the cohort.ConclusionThis study revealed that ODX-RS supported decision-making regarding postoperative adjuvant chemotherapy, especially when other tumour biomarkers, such as tumour size, grading, or Ki-67, indicated lower risk criteria. Patients with a high ODX-RS were offered chemotherapy where appropriate and its use led to a 15% rate of initial decision change in adjuvant treatment decisions; this involved either recommending chemotherapy or its omission.

Abstract 5405: Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value

Abstract Purpose: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. The expression of Cathepsin D is regulated by steroid hormones including oestrogen and growth factors. There are conflicting results between different studies regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. Furthermore, Cathepsin D has not been recommended for clinical use by the American Society of Clinical Oncology because of insufficient evidence. This study was aimed to fill the gap in the lack of recent and large studies on prognostic significance of Cathepsin D expression by studying a large well-characterized series of primary breast cancer for cathepsin D expression using immunohistochemistry. Methods: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n=954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of cathepsin D expression with clinicopathological parameters and prognosis was evaluated. Results: Cathepsin D expression was positive in 28.8% (275/954) of breast cancer tumors. Positive expression of cathepsin D was significantly associated with high histological grade (p=0.007), pleomorphism (p=0.002), poor Nottingham Prognostic Index score (NPI) (p&amp;lt;0.002), recurrence (p=0.005) and distant metastasis (p&amp;lt;0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer specific survival (BCSS) (p=0.001), higher risk of recurrence (p=0.001) and distant metastasis (p&amp;lt;0.0001). Cathepsin D positive tumors with ER positive staining who were treated with tamoxifen were associated with lower BCSS and higher risk of developing distant metastasis (p=0.001). Conclusion: This study shows Cathepsin D expression as a promising prognostic biomarker for early operable invasive breast cancer. Our results indicate that Cathepsin D expressing tumors are associated with shorter breast cancer specific survival and higher risk of recurrence and metastasis. Cathepsin D could be clinically useful to predict response to tamoxifen treatment. Targeting Cathepsin D either through inhibition of action or interference with the proteolytic pathway could be used to treat metastatic breast cancers expressing Cathepsin D. Citation Format: Inas M. Alhudiri, Christopher C. Nolan, Ian O. Ellis, Emad A. Rakha, Adam Elzagheid, Andrew R. Green, Caroline J. Chapman. Expression of cathepsin D in early-stage breast cancer and its prognostic and predictive value [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5405.

A STUDY OF PERINEURAL AND LYMPHOVASCULAR SPACE INVASION IN INVASIVE CARCINOMA BREAST PATIENTS

OBJECTIVES: To know the Perineural and lymphovascular space invasion in early operable breast cancer patients since these are prognostic factors in patient's invasive carcinoma breast. Methods: In this present study, Perineural and lymphovascular space invasion was studied pathologically in postmastectomy specimens in 134 patients. RESULTS: In this study,6 (4.48%) patients had perineural invasion and 2 (1.49%) patients had only perineural invasion without lymphovascular space invasion. 19(14.18%) patients had lymphovascular space invasion and 15 (11.2%) patients had lymphovascular space invasion alone without perineural invasion. 4(3%) patients had both lympho vascular space invasion alone and perineural invasion. CONCLUSION: Lympho vascular space invasion, which impact the prognosis adversely, is present in 15% of the patients with invasive carcinoma breast.

A phase II randomised study of preoperative trastuzumab alone or combined with everolimus in patients with early HER2-positive breast cancer and predictive biomarkers (RADHER trial)

IntroductionResistance to trastuzumab in breast cancer is an ongoing challenge. Clinical and biological effects of co-targeting HER2 and mammalian target of rapamycin (mTOR) in patients with HER2-positive early operable breast cancer via the addition of everolimus to preoperative trastuzumab were evaluated in a phase II randomised study. MethodsPatients were randomised 1:1 to receive trastuzumab (4 mg/kg initial dose then 2 mg/kg weekly for 5 weeks) alone or combined with everolimus (10 mg/day for 6 weeks) and then underwent surgery. Tumours were assessed by clinical examination and echography at the baseline and on treatment. The primary end-point was the clinical response rate at 6 weeks. Pathological response and safety were also evaluated. Baseline and surgery tumour samples were assessed by immunohistochemistry and multiplex immunoanalysis for predictive downstream effectors of the PI3K/AKT/mTOR and MAP kinase (MAPK) pathways. ResultsEighty-two patients were enrolled, 41 per arm. The clinical response rates were 34.1% and 43.9% with trastuzumab alone and combined with everolimus, respectively. Pathological response rates were 43.6% and 47.5%, respectively. Addition of everolimus increased toxicity, notably mucositis (82.5% versus 5.0%) and rash (57.5% versus 10.0%), but grade III/IV events were rare. No correlation between response to treatments and baseline candidate biomarkers was identified, except for PIK3CA mutations which were found to predict trastuzumab resistance. Significant changes were seen in several MAPK pathway effectors after combination therapy. ConclusionsThe addition of everolimus did not improve the efficacy, but induced MAPK signalling. Combination therapy to overcome pathway cross-talk should be considered to maximise the effectiveness of trastuzumab in this setting.ClinicalTrial.gov Identifier NCT00674414.

Cost-effectiveness analysis of intraoperative radiation therapy versus external beam radiation therapy for the adjuvant treatment of early breast cancer: A systematic review.

Background: Breast-conserving surgery (BCS) is the recommended treatment for early breast cancer. After BCS. Whole-breast external beam radiotherapy (WB-EBRT) is the standard of care. A possible alternative to post-operative WB-EBRT is intraoperative radiation therapy (IORT). The objectives of this systematic review were to analyses the cost-effectiveness of IORT versus EBRT for early-stage breast cancer and to assess the reporting quality of the included studies to inform future studies. Methods: A systematic literature search was carried out in five main databases (PubMed, Scopus, Embase, Cochrane library, and Web of Science) to identify original studies published to June 25, 2020. We included all full economic evaluation studies (cost-effectiveness analysis (CEA), cost-utility analysis (CUA), and cost-benefit analysis (CBA), Model-based or trial-based) that assessed and compared IORT and EBRT in patients with early operable breast cancer. Study outcomes included cost per life-years gained or cost per quality-adjusted life-years (QALYs) gained or in monetary units or incremental cost-effectiveness ratio (ICER). The quality of the included articles was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. This review has been conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Of 1155 studies identified, eight studies met the inclusion criteria. In four studies, IORT was associated with lower costs and higher effectiveness than EBRT. In three studies, the dominant option was EBRT. In these studies, IORT also had lower costs and lower effectiveness than EBRT. Existing evidence suggests that IORT can be a cost-effective alternative to early breast cancer treatment by reducing therapeutic costs. Variables of cost-effectiveness were treatment costs, health state utilities, local and distant recurrence rates, and the probabilities of metastasis after treatment, recurrent cancer and death for both IORT and EBRT. The reporting quality of the included studies was "high" in five, "medium quality" in one and "low" in two studies. Conclusion: Current evidence is sparse, and the number of studies was small but this evidence proposes that IORT can be a potential cost-saving strategy to the health systems for the adjuvant treatment of early breast cancer if the technology was carried out routinely in eligible patients. However, these results should be interpreted with caution because of the heterogeneity of studies and possible publication bias.

Low-cost Fluorescein as an Alternative to Radio-colloid for Sentinel Lymph Node Biopsy-a Prospective Validation Study in Early Breast Cancer.

Sentinel lymph node biopsy (SLNB) using radio-pharmaceutical (RP) and a blue dye is gold standard for axillary staging in clinically node-negative early breast cancer. High costs and limited availability of RP and/or gamma probe are major deterrents in performing SLNB in developing countries. Fluorescence-guided SLNB can obviate the need for RP and gamma probe. Fluorescein is an inexpensive fluorescent lymphatic tracer. In this study, we compared SLN identification rate (SLN-IR) and false negative rates (FNR) of fluorescein-guided SLNB and radio-guided SLNB using 99mTc-Sulfur-colloid, in isolation, or in combination with methylene blue dye (MBD). Sixty-five cN0 early and large operable breast cancer patients underwent validation SLNB using fluorescein (and blue LED light), 99mTc-Sulfur-colloid (and gamma probe) and MBD. Inj Fluorescein 4% was injected, 1ml each peri-tumoral and sub-areolar five minutes before axillary incision. Axillary dissection was performed irrespective of SLNB histology. The SLN-IR and FNR with various tracers and their combinations were compared. The mean number of SLNs identified was 3.5 ± 1.8 (range 1-6). The SLN-IR using RP alone was 94%, fluorescein alone was 92%, and MBD alone was 82%. The SLN-IR using fluorescein plus MBD combination was 95.4%, compared to 97% using MBD plus RP combination. FNR was 6.3% using fluorescein plus MBD, as well as RP plus MBD combinations. SLN-IR of > 90% and SLN-FNR of < 10% using fluorescein plus MBD combination are in acceptable range, and are comparable to that of RP plus MBD combination. Fluorescein can replace RP for performing SLNB, in combination with MBD.

Abstract P2-14-10: Prosigna® test in clinical routine: Impact on adjuvant chemotherapy decision and medico-economic considerations in France

Abstract The Prosigna® test has been performed in Institut Curie, France, since 2016 in clinical routine with a financial support of the health ministry dedicated to innovative procedures. The genomic platform at the Institut Curie performs the Prosigna® test for patients cared for at the Curie Hospital and in other institutions. Our main objective was to evaluate the impact of Prosigna® tests on adjuvant chemotherapy decisions. The second objective was to assess the costs associated with implementation of the test for patient management. Methods: Early breast cancer patients with estrogen receptor positive and human epidermal growth factor receptor 2-negative tumors, who had a Prosigna® test in clinical routine, were prospectively registered and observed. The Prosigna® test was indicated for a population candidate for a chemotherapy, with an intermediate risk of recurrence defined by our regional guidelines (1): grade 1 T1cN1, grade 1 T2N0-1, grade 2 T1cN0 with risk factors (Ki67&amp;gt;20% or lympho-vascular emboli), grade 2 T2N0, grade 3 T1cN0. The French Health Authority (FHA) has also recently defined the population who are candidates for genomic testing: T1c/T2 and N0/N1(mic) and grade 2 without risk factors (age&amp;lt;40, lympho-vascular emboli, T2; association of at least 2 criteria). To evaluate the decision impact of Prosigna® test, we compared the number patients recommended for chemotherapy before and after the test, in both the full real-life population and in the population defined by FHA. To evaluate costs, we compared the use of the test and the direct medical and non-medical costs of chemotherapy avoidance after tests results. All costs were considered at a National Health Insurance perspective. Genomic tests are reimbursed 1,849.50€. We previously evaluated the direct costs of the first year of management of early operable breast cancer including medical costs and non-medical costs (transportation, daily allowance), in a prospective study (2,3, ClinicalTrials.gov identifier: NCT02813317). The total added direct costs of chemotherapy were 9,737€/ patient. Results: Prosigna® test was performed for 831 patients in clinical practice from 2016 and 2019 at Institut Curie. Due to missing data, analyses have been performed on 735 patients. Median age was 57 years-old (28-80), and median size 18 mm (3-80). We observed a majority of grade 2 tumors (n=572, 78%), and 21% of lymph node involvement. Median Ki67 was 20 (0-100). Prosigna® tests classified respectively 234 (32%), 295 (40%) and 206 (28%) in high, intermediate and low risk categories. In the all real-life population (n=735), chemotherapy was avoided for 308 (42%) patients after Prosigna® test results, and in 192 (44%) cases in the population defined by the FHA (n=433). From a financial point of view, both the real-life data and the population defined by FHA demonstrated cost savings,1 739 614€ (n=735 patients). and 1 068 671€(n=433), respectively. Conclusion: This large real-life study showed a 40% decrease in adjuvant chemotherapy recommendations after introduction of the Prosigna® test in a population of chemotherapy candidates. Moreover, this therapeutic de-escalation demonstrated an overall cost savings for the health system despite the added cost of the test.

Evaluation of Diagnostic Accuracy and Impact of Preoperative Positron Emission Tomography/Computed Tomography in the Management of Early Operable Breast Cancers.

Aim:Our aim of this study was to evaluate the diagnostic accuracy of staging positron emission tomography/computed tomography (PET/CT) in early breast cancers (EBCs) and to assess its impact on disease management.Patients and Methods:We retrospectively reviewed preoperative PET/CT scans of patients from January 2015 to December 2018 with Stage I/II, clinically T1–T2 N0–N1 breast cancers. The diagnostic performance of PET/CT for nodal (N) and distant metastases (M), its correlation with patient/tumor-specific factors, and its impact on disease management were analyzed using histopathology/clinical follow-up as standards of reference.Results:Of 158 patients evaluated, 14% of patients were Stage I (T1N0), 60% were Stage IIA (T1N1, T2N0), and 26% were Stage IIB (T2N1). Sensitivity, specificity, and the diagnostic accuracy of PET/CT for axillary staging were 76%, 97%, and 84% and for distant metastasis evaluation were 100%, 98%, and 99%, respectively. The diagnostic accuracy of PET/CT for axillary staging was lower for low-grade, T1 tumors, postmenopausal group, and luminal A pathological subtype (77%, 84%, 81%, and 73%, respectively) compared to high-grade, T2 tumors, premenopausal group, and nonluminal A subtype (88%, 88%, 94%, and 87%, respectively). Distant metastases were detected on PET/CT in overall 16% (n = 25) of the patients (9% in Stage IIA and 27% in Stage IIB). PET/CT also incidentally identified clinically occult internal mammary nodes in 5% (n = 8) and organ-confined synchronous second malignancies in 5% (n = 8) of the patients.Conclusion:Preoperative PET/CT should be considered in all EBCs> 2 cm as it upstages the disease and alters management in about 24% of these patients. Given its high specificity for axillary staging PET/CT, patients with PET-positive axilla can be subjected to axillary dissection and those with PET-negative axilla to sentinel lymph node biopsy. The yield and diagnostic accuracy of PET/CT is less for low-grade tumors <2 cm and with luminal A subtype.

Human Epidermal Growth Factor-2 Receptor [HER2] Status in Patients Aged 70 years or more with Operable Early Breast Cancer — Multicentre Based Study with Review of 150 Cases

Background: Breast cancer is the most common invasive cancer in females but often has more favourable tumour biology in the older age group. More than 30% of those diagnosed with breast cancer worldwide are aged ≥ 65. Some report this percentage to be even higher, reaching up to more than 50% in developed countries that have a longer overall life expectancy. Within this group, hormone receptor-positive and human epidermal growth factor-2 (HER-2) negative are the most favourable tumour biological patterns. In contrast, the triple-negative breast cancer group has the worst prognosis. Invasive breast cancers in younger age groups have a more poorly differentiated histological grade, more hormone receptor-negative status, a remarkable extent of lympho-vascular invasion and a greater expression/amplification of HER-2 than older age groups. HER-2 receptor is amplified and over-expressed in about 20–30% of invasive breast cancers within all age groups. To analyse the status of HER-2 receptors early invasive breast cancer in relation to the histological subtype in the older age group. Methods: The study group includes 150 patients with early breast cancer . The patho-morphological data and immune-histochemistry results of invasive cancer have been analysed, this included histology subtype, grade, oestrogen/progesterone receptor status as well as HER-2 expression. Results: HER-2 expression was only seen in 17% of cases, it was seen mainly in Grade 3 cancers (9%), followed by Grade 2 (6%), with Grade 1 cancer accounting for only 1% of the study group. Conclusions: Patients with breast cancer aged ≥ 70 are seen to have less aggressive biology and expression of HER-2 receptors.

Taxanes for adjuvant treatment of early breast cancer.

Taxanes for adjuvant treatment of early breast cancer.

Direct medical and non-medical costs of a one-year care pathway for early operable breast cancer: Results of a French multicenter prospective study.

IntroductionThe organization of health care for breast cancer (BC) constitutes a public health challenge to ensure quality of care, while also controlling expenditure. Few studies have assessed the global care pathway of early BC patients, including a description of direct medical costs and their determinants. The aims of this multicenter prospective study were to describe care pathways of BC patients in a geographic territory and to calculate the global direct costs of early stage BC during the first year following diagnosis.MethodsOPTISOINS01 was a multicenter, prospective, observational study including early BC patients from diagnosis to one-year follow-up. Direct medical costs (in-hospital and out-of-hospital costs, supportive care costs) and direct non-medical costs (transportation and sick leave costs) were calculated by using a cost-of-illness analysis based on a bottom-up approach. Resources consumed were recorded in situ for each patient, using a prospective direct observation method.ResultsData from 604 patients were analyzed. Median direct medical costs of 1 year of management after diagnosis in operable BC patients were €12,250. Factors independently associated with higher direct medical costs were: diagnosis on the basis of clinical signs, invasive cancer, lymph node involvement and conventional hospitalization for surgery. Median sick leave costs were €8,841 per patient and per year. Chemotherapy was an independent determinant of sick leave costs (€3,687/patient/year without chemotherapy versus €10,706 with chemotherapy). Forty percent (n = 242) of patients declared additional personal expenditure of €614/patient/year. No drivers of these costs were identified.ConclusionInitial stage of disease and the treatments administered were the main drivers of direct medical costs. Direct non-medical costs essentially consisted of sick leave costs, accounting for one-half of direct medical costs for working patients. Out-of-pocket expenditure had a limited impact on the household.

Clinical value of CTC in predicting the efficacy of treatment in breast cancer.

e12104 Background: Circulating tumor cells (CTCs) have proven to be underlying surrogate markers for several cancers. We aimed to investigate the diagnostic, predictive, and prognostic value of tCTCs using a four-CTC marker (CK19, surviving, Her2 and MUC1) real-time quantitative PCR (RT-PCR) assay in patients with breast cancer. Methods: In a previous study, we established a multimarker RT-PCR platform to detect and quantify CTC in colorectal cancer. By choosing four mRNA markers (CK-19/surviving/Her2/Muc1), we quantified CTC in the peripheral blood of 90 early operable breast cancer patients, 40 patients who had undergone surgery and received 6 cycles of follow-up of neoadjuvant chemotherapy, and 30 healthy volunteers. For early operable breast cancer patients, the CTC status at preoperative and postoperative time points was monitored. For the other 40 patients undergoing systemic adjuvant chemotherapy, the CTC status at six or more different time points was monitored. Results: CTCs were detected in 81% (73/90) of patients with early operable breast cancer. After surgery, 67.1% (49/73) of the patients switched to negative status. 36 out of 40 (90%) patients who received systemic adjuvant chemotherapy were CTC-positive. During follow-up, 31 out of 36 (86%,) patients became CTC-negative after 4 chemotherapy cycles. Among these 36 patients, four patients had relapsed within one year, and one had died. Three out of four relapsed patients, including the deceased one, switched into high CTC-positive status before diagnosed recurrence. Conclusions: The decrease of the levels of these CTC mRNA markers after surgery indicates that these CTC markers could be used as an indirect evaluation of tumor burden. The level of CTC mRNA markers could also help to evaluate therapeutic efficacy and disease progression.

Impact of serum vitamin D on the response and the prognosis in breast cancer patients treated with neoadjuvant chemotherapy.

e12088 Background: Neoadjuvant chemotherapy (NAC) is one of the standard therapeutic strategies for operable early breast cancer (BC). A relationship between chemotherapy response and the prognosis has been suggested, especially in HER2+ or triple negative breast cancer (TNBC). Recently, the impact of vitamin D (VD) on pathological complete response (pCR) after NAC has been reported, however, there are no data regarding the relationship between VD level and the efficacy of NAC in Japanese BC patients. Methods: This study included 236 patients with BC at clinical stage I-III, who were treated with anthracycline and taxane-based NAC. HER2-directed therapies were used for HER2+ tumors. Serum 25, hydroxyl VD levels were evaluated using by ELISAusing blood samples obtained before NAC. VD deficiency was defined as &lt;20 ng/ml. Results: Pathological complete response (pCR) was obtained in 52 patients (22.0%). The pCR rate was significantly higher in the patients with HER2+ or TNBC compared with hormone receptor (HR)+/HER2-tumors (p&lt;0.0001). Median VD level was 10.7 ng/ml, and only 7 patients (3.0%) had a VD level ≥20 ng/ml. These results show that most Japanese women are deficient for VD. VD levels increase with age, and the VD levels are significantly higher in postmenopausal patients than in the premenopausal patients (p=0.0029). Patients were dichotomized into VD-low and -high groups at the median value (10.7 ng/ml). Serum VD was not associated with pCR in the all cohort, however, pCR rate was higher in VD-high group in premenopausal patients, especially in the patients withHER2+ or TNBC (p=0.0328). High VD was significantly associated with better prognosis in terms of relapse-free survival (p=0.0327) and distant metastasis-free survival (p=0.0051). This association was observed both in pre- and post-menopausal patients, especially in the patients with HER2+ or TNBC. Conclusions: High VD levels were associated with high pCR rate in premenopausal patients with HER2+ or TNBC. High VD levels were also associated with better prognosis operable BC patients treated with NAC, although VD levels of most Japanese BC patients were lower than the cut-off value.

Efficacy of two-weekly nanoparticle albumin-bound paclitaxel as neoadjuvant chemotherapy for breast cancer.

Aim: Compare the two-weekly regimens of nanoparticle albumin-bound paclitaxel (nab-P) with solvent-based paclitaxel (sb-P) as neoadjuvant chemotherapy for breast cancer. Materials & methods: Patients (n=162) with operable early breast cancer received four cycles of dose-dense epirubicin and cyclophosphamide followed by four two-weekly cycles of nab-P (n=83) or sb-P (n=79), with trastuzumab when needed. Results: Across all the patients, the ypT0 ypN0 and ypT0/is ypN0 pathological complete response rates in the nab-P group were not superior to those in the sb-P group. However, pathological complete response rates for triple-negative breast cancer were significantly better with nab-P than with sb-P. Meanwhile, nab-P also induced more peripheral sensory neuropathy. Conclusion: The two-weekly nab-P regimen is a good neoadjuvant chemotherapy choice for triple-negative breast cancer.

Pharmacokinetic and exploratory exposure\u2013response analysis of pertuzumab in patients with operable HER2-positive early breast cancer in the APHINITY study

PurposeTo characterize the pharmacokinetics (PK) of, and perform an exploratory exposure–response (E–R) analysis for, pertuzumab in patients with HER2-positive early breast cancer (EBC) within the APHINITY study (NCT01358877, BIG 4–11/BO25126/TOC4939G).MethodsA previously developed pertuzumab two-compartment linear population pharmacokinetic (popPK) model was subjected to external validation to examine appropriateness for describing pertuzumab concentrations from the APHINITY study. Pharmacokinetic drug–drug interactions (DDIs) between pertuzumab, trastuzumab, and chemotherapy were assessed by comparing observed serum or plasma Cmax, Cmin, and AUClast geometric mean ratios with 90% CIs. Predictions of pertuzumab Cmax,ss, Cmin,ss, and AUCss were derived from individual parameter estimates and used in an exploratory E–R analysis.ResultsUsing data from 72 patients, based on goodness-of-fit, the popPK model was deemed appropriate for predictions of individual exposures for subsequent comparisons to historical data, assessment of DDIs, and E–R analyses. No evidence of DDIs for pertuzumab on trastuzumab, trastuzumab on pertuzumab, or pertuzumab on chemotherapy PK was observed. Analyses of differences in exposure between patients with and without invasive disease-free survival events did not indicate improved efficacy with increased exposure. Overall Grade ≥ 3 diarrhea prevalence was higher with pertuzumab versus placebo, but was not greater with increasing pertuzumab exposure. No apparent E–R relationship was suggested with respect to other grade ≥ 3 AEs.ConclusionOverall, the limited available data from this exploratory study suggest that no dose adjustments are needed for pertuzumab when administered in combination with trastuzumab and an EBC chemotherapy regimen.