Therapy For Early-stage Breast Cancer Research Articles

Changes in Intratumor Blood Flow After Carbon-Ion Radiation Therapy for Early-Stage Breast Cancer

PurposeThis study aimed to quantify the changes in intratumoral blood flow after carbon-ion radiation therapy (CIRT) for early-stage breast cancer and analyze their clinical significance. Patients and MethodsWe included 38 patients with early-stage breast cancer who underwent CIRT. Dynamic imaging was performed using a 3T superconducting magnetic resonance scanner to quantify the washin index (idx), which reflects contrast uptake, and washout idx, which reflects the rate of contrast washout from tumor tissue. The changes in the apparent diffusion coefficient, washin idx, and washout idx were examined before CIRT and at 1 and 3 months after treatment. Clinical factors and imaging features were examined using univariate and receiver operating characteristic curve analyses to identify factors predicting clinical complete response (cCR). ResultsThe median observation period after CIRT was 51 (range: 12-122) months. During the observation period, 31 of the 38 patients achieved cCR, and 22 achieved cCR within 12 months. Tumor size (P < .001), washin idx (P = .043), and washout idx (P < .001) decreased significantly 1-month after CIRT. In contrast, the apparent diffusion coefficient values (P < .001) increased significantly 1-month after CIRT. Univariate analysis suggested that the washin idx after 1 and 3 months of CIRT was associated with cCR by 12 months post-CIRT (P = .028 and .021, respectively). No other parameters were associated with cCR by 12 months post-CIRT. Furthermore, receiver operating characteristic curve analyses showed that the area under the curve values of washin idx after 1 and 3 months of CIRT was 0.78 (specificity 75%, sensitivity 80%) and 0.73 (specificity 75%, sensitivity 71%), respectively. ConclusionTumor changes can be quantified early after CIRT using contrast-enhanced magnetic resonance imaging in patients with breast cancer. Washin idx values 1 and 3 months after CIRT were associated with cCR within 12 months post-CIRT.

Cost-effectiveness of one-year adjuvant trastuzumab therapy in treatment for early-stage breast cancer patients with HER2+ in Vietnam.

In Vietnam, trastuzumab is included in social health insurance's benefits package with a reimbursement rate of 60%, but policymakers have been concerned about its cost-effectiveness. The research aims to evaluate the cost-effectiveness of one-year adjuvant trastuzumab therapy for early-stage breast cancer patients with human epidermal growth receptor 2 (HER2+) from a societal perspective. A Markov model was developed and validated to estimate the lifetime cost and effectiveness (using life year and quality-adjusted life year) of one-year adjuvant trastuzumab therapy compared to chemotherapy (using paclitaxel) alone. Treatment efficacy and transition probabilities were estimated based on published trials (i.e., N9831, NSABP B-31, HERA, and BCIRG 006). Local cost and utility data were employed to capture the Vietnam context. One-way sensitivity analysis, probabilistic sensitivity analysis, threshold, and scenario analysis were also performed. One-year adjuvant trastuzumab therapy combined with chemotherapy compared to chemotherapy alone yielded an additional cost of 888,453,971VND (39,062 US$) with an additional 3.09 LYs and 1.61 QALYs, resulting in an ICER of 287,390,682 VND (12,635 US$) per LY gained, or 519,616,972 VND (22,845 US$) per QALY gained. The ICER exceeds the cost-effective threshold of 1- and 3-time GDP per capita by 6.3 and 2.1 times. The probabilistic sensitivity analysis shows similar results. According to one-way sensitivity analysis, ICERs were driven mainly by transition probabilities and trastuzumab price. One-year adjuvant trastuzumab therapy would be cost-effective at the 3-time GDP per capita threshold if the cost of Herceptin 150mg and 450mg vials were reduced by 56% and 54%, correspondingly. In Vietnam, one-year adjuvant trastuzumab therapy for early-stage breast cancer with HER2+ is not cost-effective. The research provided reliable and updated evidence to support policymakers in revising the health insurance benefit package. The policymakers should consider the options to reduce the cost of trastuzumab (e.g., regarding the use of trastuzumab biosimilars, price negotiation options, and options of optimizing the use of Herceptin vials among concurrent hospitalized breast cancer patients).

Exploration of immune checkpoint inhibitors in neoadjuvant therapy of early-stage breast cancer.

Exploration of immune checkpoint inhibitors in neoadjuvant therapy of early-stage breast cancer.

A Prospective Trial of Single-Fraction Radiation to the Tumor Bed with a Novel Breast-Specific Stereotactic Radiation Therapy Device: The GammaPod

IntroductionRadiation therapy for early-stage breast cancer is typically delivered in a hypofractionated regimen to the whole breast followed by a tumor bed boost. This results in a treatment course of approximately 4 weeks. In this study, the tumor bed boost was delivered in a single fraction as part of a safety and feasibility study for FDA clearance of the device. Materials and MethodsEligible women with early-stage breast cancer underwent lumpectomy followed by radiation therapy. Patients underwent breast immobilization using a system specific for the GammaPod followed by CT simulation, boost treatment planning, and boost treatment delivery all in a single treatment day. Patients then started whole-breast radiation therapy within 1 week of the boost treatment. Patients and treatments were assessed for safety and feasibility. Acute toxicities were recorded. ResultsA single-fraction boost of 8 Gy was delivered to the tumor bed prior to a course of whole-breast radiation. The GammaPod treatment was successfully delivered in 14 of 17 enrolled patients. Acute toxicities from all radiation therapy, inclusive of the boost and whole-breast radiation, were limited to grade 1 events. ConclusionThe GammaPod device successfully delivered a single-fraction boost treatment to the tumor bed with no change in expected acute toxicities. The results of this study led to FDA clearance of the device through the Investigational Device Exemption process at the FDA. The GammaPod is in clinical use at 4 institutions nationally and internationally, with an additional sites pending in 2023.

Women's Preferences for Hypofractionated Radiation Therapy for Treatment of Early-Stage Breast Cancer: A Discrete Choice Experiment

IntroductionThe primary treatment recommended for early-stage breast cancer is breast conserving surgery followed by external beam radiation therapy of the whole breast. Previously radiation therapy for early-stage breast cancer was given using more fractions over longer durations. Guidelines support treatments with fewer fractions over a shorter time (hypofractionated radiation therapy-HFRT). This study aimed to understand women's preferences for different features of treatments for early-stage breast cancer. MethodsA discrete choice experiment (DCE) with 12 choice tasks was conducted, describing the treatments by: extent of surgery, duration of radiation treatment, need to relocate for treatment, local side effects, changes in breast appearance, costs, and difficulty with daily activities during and after treatment. Participants were women with breast cancer and from the general population. Mixed logit analyses were conducted and trade-offs between attributes estimated. Results420 respondents completed the DCE. The relative importance of attributes varied by respondent characteristics; the most influential attribute for younger women was type of surgery (breast conserving surgery); type of surgery did not influence older women's preferences. Shorter treatment duration, avoiding relocation, fewer local side effects, and less difficulty with daily activities all positively influenced treatment preference. Younger women were willing to accept 32-40 days of radiation treatment before a treatment that included mastectomy was potentially acceptable. Conclusionattributes of treatment such as duration, need for relocation, side effects and impacts on normal daily activities during and after treatment significantly influenced women's preference for treatment, including surgery. Our findings have the potential for real impact for patients and services including supporting one on one clinical discussions, supporting program and patient resource development, and by informing service funding, organisation and delivery.

Fine-Tuning Adjuvant Endocrine Therapy for Early-Stage Breast Cancer: An Expert Consensus on Open Issues for Future Research.

After decades of research, improving the efficacy of adjuvant endocrine therapy (ET) for early-stage breast cancer becomes increasingly difficult. Beyond technological breakthroughs and the availability of new classes of drugs, further improvement of adjuvant ET will require applying a rigorous research approach in poorly investigated areas. We critically discuss some key principles that should inform future research to improve ET efficacy, including identifying specific subgroups of patients who can benefit from escalating or de-escalating approaches, optimizing available and new treatment strategies for different clinical contexts, and dissecting the direct and indirect biological effects of therapeutic interventions. Four main issues regarding adjuvant ET were identified as relevant areas, where a better application of such principles can provide positive results in the near future: (i) tailoring the optimal duration of adjuvant ET, (ii) optimizing ovarian function suppression for premenopausal women, (iii) dissecting the biological effects of estrogen receptor manipulation, and (iv) refining the selection of patients to candidate for treatments escalation.

Five Fraction Accelerated Partial Breast Irradiation Versus Intraoperative Radiation Therapy for Early-Stage Breast Cancer

Purpose/Objective(s)Accelerated partial breast irradiation (PBI) delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable clinical outcomes to whole breast irradiation with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were promising, concerns exist regarding long-term rates of local recurrence after IORT. We present a comparison of 5 fraction PBI versus IORT. Materials/MethodsWe performed a retrospective review of 473 patients with early-stage breast cancer treated at a single institution from 2011 to 2021 with 258 receiving PBI and 215 receiving IORT. PBI patients received 30 Gy in 5 fractions delivered with IMRT. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface at surgery using the low-energy TARGIT technique. ResultsMean age was 71 years old (IQR:67-74) for IORT patients and 67 years old (IQR:62-72) for PBI patients. Median follow up was 5.7 years (IQR:4.2-7.0) for IORT patients and 2.4 years (IQR:1.8-3.3) for PBI patients (P < .001). Recurrence at any time (locoregional and distant) was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving PBI. IORT was associated with reduced rates of locoregional relapse free survival at 5 years (93.6% vs. 99.4%, P = .05) with no difference in overall survival(92.8% vs. 95.1%, P = .99). ConclusionLow-energy TARGIT IORT was associated with higher rates of locoregional recurrence compared to PBI. These outcomes, consistent with other series and current guidelines, suggest a limited role for low-energy IORT as monotherapy.

Intraoperative Radiation Therapy for Early-Stage Breast Cancer: Updated Outcomes from a Single-Institution Experience.

Increasingly, data have supported the use of partial-breast irradiation (PBI) for low-risk patients after breast-conserving surgery, with techniques allowing for completionof treatment in 1-3 weeks. Intraoperative radiation therapy (IORT) is an alternative to PBI. Ourinstitution hadused low-energy photon IORT (TARGIT) for more than a decade. The initial results demonstrated a 2% local recurrence rate witha short follow-up period of 2 years. This report presents updated outcomes during with5-year follow-up. A review of an institutional review board (IRB)-approved institutional registry was performed. The review identified 215 patients with early-stage breast cancer (stages 0-IIA) who received IORT. At the time of surgery, IORT was delivered with20Gy in a single fraction, with 5.1% (n = 11) of patients receiving additional whole-breast irradiation (WBI). The mean age at diagnosis was 71 years (range, 49-98 years), and the median follow-up was 5.7 years (interquartile range [IQR], 4.2-7.0 years). Of the 215 patients, 2.8% (n = 6) had ductal carcinoma in situ (DCIS), 90.7% (n = 195) had T1 disease, and 6.5% (n = 14) had T2 disease. Endocrine therapy was prescribed for 79% and chemotherapy for 1.4% of the patients. The 5-year rates were 5.3% for local recurrence, 6.4% for locoregional recurrence, and 2.7% for distant metastases. At 5 years, 93% of the patients were alive. The 5-year outcomes with TARGIT IORT demonstrated high rates of local recurrence, exceeding those seen with alternative modern approaches. The local recurrence outcomes with IORT are more consistent with studies omitting radiation followingbreast-conserving surgery, using endocrine therapy alone. Consistent with current guidelines and previous data, TARGIT IORT should not be used as monotherapy outside prospective clinical trials.

299P Single-cell transcriptomic analysis reveals specific luminal and T cell subpopulations associated with response to neoadjuvant therapy in early-stage breast cancer

299P Single-cell transcriptomic analysis reveals specific luminal and T cell subpopulations associated with response to neoadjuvant therapy in early-stage breast cancer

Adjuvant Breast Radiation Therapy for Early-Stage Breast Cancer or Ductal Carcinoma In-Situ in the Breast: A Systematic Review and Network Meta-Analysis of Randomized Trials

For selected patients with early-stage breast cancer (BC) or ductal carcinoma in-situ (DCIS) in the breast, adjuvant breast radiation therapy (RT) approaches include partial breast irradiation (PBI), altered fractionation (AF) whole breast irradiation (WBI) or tumor bed boost (TBB). However, it is unclear which is the optimal approach. This study aims to compare the effects of different PBI, AF-WBI and TBB options on ipsilateral breast tumor recurrence (IBTR), overall survival (OS) and patient reported cosmesis (PRC) outcomes. We searched various biomedical electronic databases for eligible randomized trials (RCTs) from date of inception to January 2023. We constructed six separate random effects frequentist network meta-analyses (NMA) to compare the effects of various PBI options using WBI as the reference; various AF-WBI options using conventional fractionated (CF) WBI as the reference and various TBB options using no TBB as the reference on IBTR and OS. The GRADE approach was used to assess the certainty of evidence. The synthesis without meta-analysis approach was pre-specified for evaluation of PRC in anticipation of various assessment and reporting methods. We included 34 RCTs comprising 49,899 participants and 11 treatment options. Evidence suggests that accelerated PBI (Hazard Ratio (HR) 1.36 (95% confidence interval (CI) 0.77 - 2.41, moderate certainty), moderately hypofractionated (MHF) PBI (HR 1.38 (0.60 - 3.19), moderate certainty) and intraoperative PBI (HR 1.47 (0.81 - 2.68), low certainty) was associated with a modest but not statistically significant increase in the hazards for IBTR when compared to WBI. There was moderate certainty evidence that there were no significant differences among the accelerated ultra-hypo fractionated (AUHF) WBI (HR 0.76 (0.50 - 1.14)), MHF-WBI (HR 0.99 (0.84 - 1.16)) or UHF-WBI (HR (1.35 (0.47 - 3.92)) when compared with CF-WBI for IBTR. The effects of sequential TBB (seqTBB) (HR 0.61 (0.52 - 0.70), high certainty) and simultaneous integrated TBB (simTBB) (HR 0.77 (0.55 - 1.09), moderate certainty) on IBTR were similar when compared to no TBB. There were no significant differences in OS between PBI options and WBI, AF-WBI options and CF-WBI, TBB options and no TBB. Among the PBI vs WBI trials, MHF-PBI and APBI may be associated with fewer adverse PRC events. Among the AF-WBI vs CF-WBI trials, half of the included trials reported fewer adverse PRC events with MHF-WBI. SeqTBB and simTBB had similar adverse PRC outcome. There were no significant differences among the PBI, AF-WBI and TBB options for IBTR and OS. PBI and AF-WBI may be associated with less adverse PRC events compared with WBI and CF-WBI respectively. There was no evidence to suggest a difference between seqTBB and simTBB for PRC outcome. This study is registered with PROSPERO CRD 42021245074.

Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types.

Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. Recurrence is still possible after mastectomy and chemotherapy and most often occurs in the first two years. We aimed to determine the mechanisms in early local recurrence in both types. Methods: We used an observational method with a cross-sectional study design. The samples were patients with early-stage IDC and ILC, who underwent modified radical mastectomy (MRM) and got adjuvant chemotherapy with taxan and anthracycline base, and experienced recurrence in the first two years after surgery. The materials in this study were paraffin blocks from surgical specimens; we examined vimentin, α-SMA and MMP1, PDGF and CD95 by immunohistochemistry (IHC). Data analysis was done using OpenEpi 3.0.1 and EZR. We used pathway analysis with linear regression. Results: There were 25 samples with local recurrence and 25 samples without recurrence in the ductal type group. The lobular type group consisted of six subjects without recurrence and seven with recurrence. There were significant differences in the expression of vimentin (p=0.000 and 0.021, respectively), PDGF (p=0.000 and 0.002) and CD95 (p=0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p=0.000) and α-SMA (p=0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: Local recurrence in early-stage IDC and ILC had different mechanisms. These findings are expected to make cancer treatment in both types more focused and efficient.

Intra-Operative Radiotherapy (IORT) in Breast Conserving Therapy in Early-Stage Breast Cancer and DCIS

Initial breast intra-operative radiotherapy (IORT) results in clinical trials were encouraging though with longer follow up, increased local recurrences have been reported compared with whole breast radiation or other partial breast radiation including accelerated partial breast irradiation (APBI) methods. The goal of the study is to report our prospective single institution IORT breast study outcomes of local recurrence (LR) including true recurrence and breast elsewhere failures, breast cancer specific survival (BCSS), and overall survival (OS) with low energy x-ray IORT in early-stage breast cancer or ductal carcinoma in situ. A total of 480 patients with early-stage breast cancer or DCIS were prospectively enrolled in an IRB approved single institution trial and treated with low energy X-ray IORT 20 Gy at time of breast-conserving surgery. Eligibility criteria included ≥ 45 years of age with unifocal tumors < 3 cm deemed candidates for partial mastectomy. Supplemental external beam radiation was recommended for patients with high-risk surgical pathology including multifocal disease, positive nodes, close margins < 2 mm, or lymphovascular invasion. Ipsilateral breast tumor recurrences were classified as true recurrence versus elsewhere failure by location and histology: same/different quadrant and similar/different histology. Kaplan-Meier methods were used to estimate survival probabilities across time. Median age of enrolled patients was 64 years with the majority of patients having favorable phenotype with 94% ER+ and 93% Her-2 - disease. 110 patients (23%) had supplemental EBRT delivered; 103 to the whole breast and 7 to the breast and regional nodes. At a median follow up of 73 months (range 17 - 131 months), there were 23 (4.8%) ipsilateral breast tumor recurrences, of which 9 were true recurrences (1.9%) and 14 elsewhere failures (2.9%). One patient with true recurrence and 3 patients with elsewhere breast failures synchronously presented with clinical or radiographic regional node involvement. Seven patient developed contralateral breast cancer and 8 patients developed distant metastases during the follow-up period. There were 2 breast cancer related deaths. At 6-years, overall survival rate was 96.8% and breast cancer specific survival was 98.7%. Our study outcomes reflect similar outcomes as other reported IORT studies with electron or low energy X-ray in breast cancer, with higher risk of local failure than historical whole breast and other partial breast radiation techniques. This supports current radiation society guidelines for IORT monotherapy for breast cancer to be optimally considered in the context of prospective clinical trials.

Five Fraction Accelerated Partial Breast Irradiation vs. Intraoperative Radiation Therapy for Early-Stage Breast Cancer

Accelerated partial breast irradiation (APBI) represents an alternative to whole breast irradiation (WBI), reducing the target volume and potentially treatment duration. APBI delivered in 5 fractions with intensity modulated radiation therapy (IMRT) has been shown to have comparable outcomes to WBI with reduced toxicity profiles. In contrast, intraoperative radiation therapy (IORT) offers patients the potential to complete adjuvant radiation therapy in a single treatment. While early data were initially promising, concerns regarding long-term rates of local recurrence exist. We present a comparison of 5 fraction APBI versus IORT. We performed a retrospective review of 473 patients with early-stage breast cancer (Stage 0-IIA) treated at a single institution with 258 receiving APBI and 215 IORT from October 2011 to May 2021. APBI patients received 30 Gy in 5 fractions delivered with IMRT daily or every other day. IORT patients received 20 Gy in 1 fraction prescribed to the applicator surface delivered at the time of surgery. Kaplan-Meier analysis was used to estimate locoregional control rates and overall survival among the 2 groups. Mean age was 70.7 years old (IQR:67-74) for the IORT patients and 66.6 years old (IQR:62-72) for the APBI patients (p<0.001). Median follow up was 5.7 years for IORT patients and 2.4 years for APBI patients (p<0.001). For IORT patients, 11%/83.5%/5.5% of patients and for APBI 17.8%/77.5%/4.7% of patients had Tis/T1/T2 disease (p = 0.005). With regards to adjuvant therapies, 79%/76% of IORT/APBI patients were offered endocrine therapy (p = 0.50) and 1.4%/6.2% chemotherapy (p = 0.008). Recurrence at any time was seen in 7.9% (n = 17) of patients receiving IORT as compared to 0.8% (n = 2) of patients receiving APBI. APBI was however no differences in recurrence free survival (92.6% vs. 98.5%, p = .079) or overall survival were noted (92.8% vs. 95.1%, p = 0.99). In a series of almost 500 patients with stage 0-IIA breast cancer, IORT was associated with higher rates of locoregional recurrence compared to APBI with no survival difference at 5 years. These outcomes, consistent with other series and current guidelines, suggest a limited role for IORT as monotherapy following breast conserving surgery.

Neratinib as adjuvant therapy in patients with HER2 positive breast cancer: expert opinion.

Neratinib is a tyrosine kinase receptor inhibitor used in the extended adjuvant therapy of early-stage breast cancer. After adjuvant trastuzumab therapy, neratinib reduces the risk of recurrence and, if taken within 1year from trastuzumab, significantly improves the invasive disease-free survival of patients with early-stage human epidermal growth factorreceptor-2 positive (HER2+) breast cancer with no increased risk of long-term toxicity. Diarrhea, the most common adverse event associated with neratinib use, deters some clinicians from prescribing this drug. However, neratinib-related toxicity is predictable, short-lived, mostly limited to the first month of treatment andcan be managed with dose-escalation and prophylactic strategies. Thus, close surveillance and prompt management, relying on supportive care and administration schedule modification, allows discontinuation of treatment to be avoided.

Immune system and tumor microenvironment in early-stage breast cancer: different mechanisms for early recurrence after mastectomy and chemotherapy on ductal and lobular types

Background: The most common type of breast cancer is the ductal type (IDC), followed by lobular type (ILC). Surgery is the main therapy for early-stage breast cancer. Adjuvant chemotherapy might be given to those at high risk of recurrence. Recurrence is still possible after mastectomy and chemotherapy and most often occurs in the first two years. We aimed to determine the mechanisms in early local recurrence in both types. Methods: We used an observational method with a cross-sectional study design. The samples were patients with early-stage IDC and ILC, who underwent modified radical mastectomy (MRM) and got adjuvant chemotherapy with taxan and anthracycline base, and experienced recurrence in the first two years after surgery. The materials in this study were paraffin blocks from surgical specimens; we examined vimentin, α-SMA and MMP1, PDGF and CD95 by immunohistochemistry (IHC). Data analysis was done using OpenEpi 3.0.1 and EZR. We used pathway analysis with linear regression. Results: There were 25 samples with local recurrence and 25 samples without recurrence in the ductal type group. The lobular type group consisted of six subjects without recurrence and seven with recurrence. There were significant differences in the expression of vimentin (p = 0.000 and 0.021, respectively), PDGF (p = 0.000 and 0.002) and CD95 (p = 0.000 and 0.045) in ductal and lobular cancer types, respectively. MMP1 (p = 0.000) and α-SMA (p = 0.000) only showed a significant difference in the ductal type. The pathway analysis showed that in the ductal type, the mechanism of recurrence was enabled by two factors: α-SMA and CD95. Meanwhile, for the lobular type, the recurrence mechanism was through the CD95 pathway. Conclusions: Local recurrence in early-stage IDC and ILC had different mechanisms.  These findings are expected to make cancer treatment in both types more focused and efficient.

Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five mammella interGruppo (MIG) and gruppo italiano mammella (GIM) randomized clinical trials (RCTs).

12067 Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( &lt; 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p &lt; .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p &lt; .006, and p &lt; .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. [Table: see text]

Neoadjuvant endocrine therapy for early-stage breast cancer: An institutional experience during the COVID19 pandemic.

e12625 Background: Neoadjuvant Endocrine therapy (NET) is under-utilized for locally advanced hormone receptor + breast cancer (BC) despite literature to date concluding that chemotherapy and NET have comparable response rates but with lower toxicity for the latter. The COVID19 pandemic presented a unique occasion to extend the use of NET for localized BC. Many surgical procedures across the country, including at Dartmouth-Hitchcock Medical Center (DHMC) were postponed in order to redirect resources. The American Society of Breast Surgeons released guidelines to manage patients in which surgery was delayed. For Estrogen Receptor + (ER+), HER2- early-stage tumors, the guidelines recommended NET as first-line treatment. Herein we review the rate of adoption of NET and patient/tumor characteristics associated with NET adoption at DHMC during the lockdown. Methods: A Retrospective analysis of patients diagnosed with early-stage ER+, HER2- BC between December 2019 and June 2020. Inclusion criteria included patients with non-metastatic hormone receptor + BC. Data extracted from chart review included age, menopausal status, tumor stage/grade, body mass index (BMI). A delay in surgery was defined as days between surgical consult and surgery over 14 days. Descriptive statistics will be applied to data collected on patient/tumor characteristics, and the number of patients accepting or declining NET. Results: 109 cases were identified within the study period with 42 cases designated as experiencing delays in surgery. The median age of the group (n = 42) was 62 and the majority was post-menopausal. 36 patients received NET with most started on an aromatase inhibitor. Median BMI was 28.5. Median duration of treatment was 39.5 days. Tumor response to NET was not clearly described in the pathology reports. Three cases were noted to have some decrease in cellularity for pathologic partial response and four had no definite response. Imaging modalities were compared to pathology size and MRI was found to be a fair predictor of size obtained from pathology specimens with a correlation metric of 0.78 indicating that it may serve as the best proxy for pre-treatment size. Pre-surgical MRIs were obtained in 51.3% of cases. The majority of patients on NET had no change in the grade of their pathology. During the course of the pandemic long-term adherence of adjuvant endocrine therapy decreased from 78% for those diagnosed in early 2020 to 56% for those diagnosed in late 2020. Conclusions: The COVID19 crisis was an unprecedented challenge to healthcare systems. Delays in surgery resulted in increased use of NET in early-stage BC. We plan to integrate other data including impact of NET on long-term adherence to endocrine therapy. Change in clinical vs pathologic stage will be reported for those with or without NET. This experience may help guide care during healthcare crises or in resources limited settings.

¿Se puede realizar la radioterapia intraoperatoria de forma asistencial en el tratamiento del cáncer de mama en estadios iniciales?

After conservative surgery in breast cancer adjuvant radiation therapy is indicated, such treatment can be performed as partial irradiation in well-selected cases and without risk factors for local relapse following the guidelines of international consensus. Partial irradiation is performed by several techniques such as interstitial brachytherapy, external radiation therapy, and also through intraoperative radiation therapy techniques at the same surgical act due to mobile electron accelerators or low-energy photons units. This allows local treatment to be performed in a single day, increasing the surgical time, but with advantages in terms of the tumor bed localization accuracy, immediacy of irradiation and greater patient satisfaction. There is extensive experience in the use of this technique with results comparable to other ways of partial irradiation in terms of local control, minimal side effects, good cosmetic results and even better no cancer related survival. This article reviews the evidence in the use of intraoperative radiation therapy in early-stage breast cancer derived from the main trials comparing it to whole breast irradiation, to confirm that it is already available for standard of care practice in patients who are candidates for partial irradiation.

Abstract P5-07-08: Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer

Abstract BACKGROUND: HER2-positive breast cancers, which accounts for 20% of breast cancers, is associated with aggressive clinical behavior and inferior survival. The approval of HER2 targeted therapy has changed the landscape of this disease and has reduced disease recurrence by 50% and has improved survival by 33%. (1) However, cardiotoxicity is a well-recognized adverse event associated with HER2-targeted therapies. Adjuvant trastuzumab emtansine (TDM1) is the current standard of care for patients with residual breast cancer after neoadjuvant HER2-targeted therapy. TDM1 is associated with a risk of cardiotoxicity defined as a decline in left ventricular ejection fraction (LVEF). In a pooled analysis of data from seven metastatic breast cancer trials with TDM1, the incidence of cardiac events such as congestive heart failure (CHF), cardiac ischemia, cardiac arrhythmia or grade 1/2 LVEF drop was 3.37%. Adjuvant breast radiation (RT) is routinely offered for patients at high risk for recurrence. Breast RT is also associated with long-term increased risk of cardiac disease more than 10 years after RT. The HERA trial which studied use of adjuvant trastuzumab showed that rates of cardiotoxicity were higher in patients receiving concurrent RT with trastuzumab (left sided &amp;gt; right sided breast cancer) compared to those who did not receive adjuvant RT, although not statistically significant. In the multivariate analysis, no treatment or baseline cardiovascular risk factors were strongly correlated with LVEF, but radiation therapy showed a borderline correlation (adjusted HR, 1.258; 95% CI, 1.00-1.58; P = .049). The risk of cardiotoxicity with concurrent TDM1 and RT has not been well studied. With increasing use of TDM1 in the adjuvant setting, it is important to understand the cardiotoxic effects of combination therapy in early-stage breast cancer. METHODS: We undertook a review of our clinical database to identify patients who received adjuvant TDM1 with concurrent RT for Stage I-III breast cancer from 1/2020 to 01/2022. Clinical parameters including age, date of diagnosis, history of cardiac disorders, echocardiogram findings, radiation dose, final pathologic stage and molecular subtypes of cancer were extracted. All patients had ejection fraction to monitor cardiac fraction. Global longitudinal strain (GLS), which is a more sensitive and reproducible indicator of cardiac dysfunction than LVEF, was also collected, if available. RESULTS: Of 32 patients identified in our retrospective analysis, two patients (6%) developed a drop in ejection fraction post radiation. Median age of patients was 57y. Majority of the patients were Caucasian (44%) followed by Hispanic (28%). 19 (60%) patients had right sided breast cancers and 13(40%) patients had left sided cancers. The mean pre-radiation ejection fraction was 60% and post radiation was 61%. Using paired t-testing, there was no statically significant difference in ejection fraction after radiation (p=0.343). Comparative GLS measurements were available for 16 patients and there was no statical difference with concurrent radiation (p=0.18). All patients tolerated radiation with mostly grade 2 skin dermatitis except four patients who had grade 3 skin dermatitis. One patient had to discontinue radiation early given grade 3 skin dermatitis. CONCLUSION: This institutional review of 32 patients suggests that adjuvant TDM1 with concurrent RT did not result in a significant change in ejection fraction or GLS. Most patients tolerated radiation without significant skin toxicities. One of the limitations of the study is the small sample size. A larger study should look at more broader conclusions; however this data has strong clinical implications. Cardiac Parameters pre and post RT Citation Format: Faheem Farooq, Dillon Cason, Nisha Ohri, Shicha Kumar, Allison Grann, Anna Litvak, Shridar Ganesan, Bruce G. Haffty, Deborah Toppmeyer, Coral Omene, Mridula A. George. Evaluating the risk of cardiotoxicity associated with concurrent trastuzumab emtansine (TDM1) and radiation therapy in patients with early-stage HER2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-07-08.

Biological and clinical review of IORT-induced wound fluid in breast cancer patients.

Intraoperative radiotherapy (IORT) has become a growing therapy for early-stage breast cancer (BC). Some studies claim that wound fluid (seroma), a common consequence of surgical excision in the tumor cavity, can reflect the effects of IORT on cancer inhibition. However, further research by our team and other researchers, such as analysis of seroma composition, affected cell lines, and primary tissues in two-dimensional (2D) and three-dimensional (3D) culture systems, clarified that seroma could not address the questions about IORT effectiveness in the surgical site. In this review, we mention the factors involved in tumor recurrence, direct or indirect effects of IORT on BC, and all the studies associated with BC seroma to attain more information about the impact of IORT-induced seroma to make a better decision to remove or remain after surgery and IORT. Finally, we suggest that seroma studies cannot decipher the mechanisms underlying the effectiveness of IORT in BC patients. The question of whether IORT-seroma has a beneficial effect can only be answered in a trial with a clinical endpoint, which is not even ongoing.