Breast Cancer Recurrence Rates Research Articles

The worldwide impact of HER2-targeted treatments in women with breast cancer: An epidemiological modeling study.

543 Background: HER2-targeted therapies (trastuzumab, pertuzumab, and T-DM1) have revolutionized the treatment and epidemiological landscape of HER2+ breast cancer, resulting in population-level increases in survival and decreases in disease recurrence. The aim of this epidemiological modeling study was to quantify the estimated global impact of HER2-targeted therapies, by estimating the number of women diagnosed with HER2+ early breast cancer (eBC) who have avoided (or will avoid) metastatic disease recurrence following treatment. Methods: We used data and projections from cancer registries, observational studies, clinical trials, and drug sales volumes (ie, utilization) to create annual country-level synthetic cohorts of patients diagnosed with HER2+ eBC, for the years 2004-2033 in 185 countries. The real-world uptake of HER2-targeted treatments and treatment flow was estimated in the main scenario. The impact of chemotherapy alone was estimated in the counterfactual scenario, assuming 100% chemotherapy worldwide. The occurrence of distant recurrences was modeled in both scenarios using weighted transitional probability averages based on invasive disease-free survival curves from clinical trials. Results: In total, during the 3-decade study period, we predicted that 11.9 million (M) women would be diagnosed with HER2+ eBC, out of which 7.5M were estimated to be treated with HER2-targeted therapies in a real-world uptake scenario. In the counterfactual scenario with only chemotherapy available, a total of 2.9M women were estimated to experience a metastatic disease recurrence, compared to only 2.1M women in the base scenario of predicted real-world uptake of HER2+ targeted therapies. This corresponds to a reduction of 26% or 768,000 women who may avoid metastatic recurrence since the introduction of HER2-targeted therapies (Table). Conclusions: HER2+ targeted therapies have substantially improved breast cancer outcomes and continue to contribute to the reduction in breast cancer recurrence rates. Further research may elucidate treatment-related reductions in costs to society as a result of population-level improvements in disease outcomes for breast cancer survivors. Given the expected rise in the burden of breast cancer globally, therapeutic advances and increased treatment utilization may further accelerate global patient benefit. [Table: see text]

Breast cancer-related lymphedema and recurrence of breast cancer: Protocol for a prospective cohort study in China.

The primary aim is to determine the factors associated with breast cancer-related lymphedema and to identify new associated factors for the recurrence of breast cancer and depression. The secondary objective is to investigate the incidence of breast cancer-related events (breast cancer-related lymphedema, recurrence of breast cancer, and depression). Finally, we want to explore and validate the complex relationship among multiple factors influencing breast cancer complications and breast cancer recurrence. A cohort study of females with unilateral breast cancer will be conducted in West China Hospital between February 2023 and February 2026. Breast cancer survivors in the age range of 17-55 will be recruited before breast cancer surgery. We will recruit 1557 preoperative patients with a first invasive breast cancer diagnosis. Consenting breast cancer survivors will complete demographic information, clinicopathological factors, surgery information, baseline information, and a baseline depression questionnaire. Data will be collected at four stages: the perioperative stage, chemotherapy therapy stage, radiation therapy stage, and follow-up stage. Data including the incidence and correlation of breast cancer-related lymphedema, breast cancer recurrence, depression, and medical cost will be collected and computed through the four stages above. For every statistical analysis, the participants will be classified into two groups based on whether they develop secondary lymphedema. Incidence rates of breast cancer recurrence and depression will be calculated separately for groups. Multivariate logistic regression will be used to determine whether secondary lymphedema and other parameters can predict breast cancer recurrence. Our prospective cohort study will contribute to establishing an early detection program for breast cancer-related lymphedema and recurrence of breast cancer, which are both associated with poor quality of life and reduced life expectancy. Our study can also provide new insights into the physical, economic, treatment-related and mental burdens of breast cancer survivors.

AB044. SOH23ABS_117. Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor positive breast cancer: a systematic review and network meta-analysis

AB044. SOH23ABS_117. Value of the 21-gene expression assay in predicting locoregional recurrence rates in estrogen receptor positive breast cancer: a systematic review and network meta-analysis

Abstract P4-03-18: Group-based trajectories of endocrine therapy adherence and risk of recurrence in a Danish premenopausal breast cancer cohort

Abstract Background: Adjuvant endocrine therapy (AET) approximately halves the risk of recurrence among the two-thirds of premenopausal breast cancer patients whose tumors overexpress the estrogen receptor (ER+). AET is recommended for a minimum five-year duration, but many premenopausal women discontinue AET prematurely. Adherence to AET is dynamic and influenced by many behavioral, societal, clinical, and genetic factors. Describing longitudinal patterns of AET adherence is an important first step towards identifying patients at highest risk of nonadherence–-and therefore recurrence–-who may benefit from adherence-enhancing interventions. We used group-based trajectory models to (1) describe AET adherence patterns, and (2) estimate associations between AET adherence and breast cancer recurrence in a Danish premenopausal, ER+ breast cancer cohort. Methods: Our cohort included 4,487 premenopausal women diagnosed with ER+, stage I–III primary breast cancer registered in the Danish Breast Cancer Group (DBCG) clinical database and treated with AET (2002–2011). We followed all patients from initiation of AET until recurrence, mortality, 10 years of follow-up, another primary malignancy, or the end of available follow-up. We excluded individuals with less than 1.5 years of follow-up as breast cancer recurrences that occur in this time are unlikely to be related to AET. At semi-annual follow-up visits, women were registered as having received (or not) a six-month supply of AET. We created daily indicators to determine if a woman had at least 80% of days covered by an AET fill within each six-month period for the first 4.5 years following AET initiation, yielding 9 variables indicating time-varying adherence. We used these indicators to characterize adherence trajectory groups. We defined recurrence as local, regional or distant metastases or contralateral breast cancer registered in the DBCG using follow-up data through 2017. We fit Cox regression models, adjusted for age and clinical factors, to estimate the association between adherence trajectory groups and recurrence. Results: We identified distinct trajectory groups in the cohort (Table 1)—high adherence (69%), slow decline (23%), and quick decline (8%). Women with quick decline were more likely to have stage I disease, have no positive lymph nodes, to not be treated with chemotherapy, and to have lumpectomy instead of mastectomy when compared to women with high adherence. Compared with high adherence women, the estimated rate of breast cancer recurrence was higher among those with slow decline (HR=1.12, 95%CI=1.04–1.21) and those with quick decline (HR=1.38, 95%CI=1.22–1.56). Conclusions: Group-trajectory modeling facilitated empirical description of AET adherence patterns in a premenopausal breast cancer cohort. As expected, women who more rapidly became AET-nonadherent were at increased risk of breast cancer recurrence compared with those who remained adherent. Future analyses will explore the contribution of specific socioeconomic, genetic, and clinical factors to AET adherence patterns, which will inform the design of interventions to improve AET adherence and reduce recurrence risk in breast cancer patients. Table 1. Trajectory group and the observed proportion of individuals adherent to their adjuvant endocrine therapy (AET) over 4.5 years of follow-up Citation Format: Kirsten M. Woolpert, Julie A. Schmidt, Thomas P. Ahern, Timothy L. Lash, Lindsay J. Collin, Bent Ejlertsen, Deirdre Cronin-Fenton. Group-based trajectories of endocrine therapy adherence and risk of recurrence in a Danish premenopausal breast cancer cohort [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 P4-03-18.

Effectiveness of Prophylactic Mastectomy

Introduction: The growing incidence and recurrence rate of breast cancer has influenced multiple strategies such as surgical interventions that serve as preventive measures for women at high risk. Prophylactic mastectomy seems to be the most effective tool in the primary prevention of breast cancer, but opinions are not uniform, especially among specialists. The goal of this presentation is to examine the effect of risk-reducing mastectomy, including breast cancer incidence, breast cancer mortality, disease-free survival, physical morbidity, and psychosocial outcomes in cohort of patients who underwent prophylactic mastectomy. Materials and Methods: We retrospectively reviewed the outcomes of 20 years of experience with prophylactic mastectomies performed at the department from 1999 to 2019. In this study were included patients who underwent bilateral prophylactic mastectomy with no breast cancer, and patients with breast cancer, if they underwent contralateral risk-reducing mastectomy, however, only the prophylactic side was considered in the analysis. Patients with bilateral breast cancer were excluded. Results: A total of 749 risk-reducing prophylactic mastectomy in 545 patients were performed at our department from 1999 to 2019. Bilateral prophylactic mastectomies were performed in 204 patients (37,4%), and 341 (62,6%) underwent a unilateral risk-reducing mastectomy secondary to cancer in the contralateral breast. Overall, 243 patients with BRCA1 mutations and 113 with BRCA2 mutations were included. Conclusion: Prophylactic mastectomy is highly preventive against breast cancer. Although further clinical studies are needed to determine the effectiveness of prophylactic mastectomies in individual indications. With the effectiveness of prophylactic mastectomy should also be taken into consideration the quality of life after the immediate breast reconstruction, and the associated complications.

Abemaciclib: A Review in Early Breast Cancer with a High Risk of Recurrence.

Abemaciclib [Verzenio® (USA) or Verzenios® (EU)] is a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor approved in combination with adjuvant endocrine therapy for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-), node-positive, early breast cancer with a high risk of recurrence. In a phase III trial, abemaciclib plus endocrine therapy reduced the risk of recurrence of breast cancer compared with endocrine therapy alone, including in patients who had previously received neoadjuvant chemotherapy, in patients with high- and low-scoring Ki-67 tumours, and in both premenopausal and postmenopausal patients. The tolerability profile of abemaciclib plus endocrine therapy was acceptable and manageable, with diarrhoea, infections and neutropenia being the most common adverse events. Thus, abemaciclib in combination with standard endocrine therapy is a valuable additional treatment option for patients with HR+, HER2-, node-positive early breast cancer with a high risk of recurrence.

Characteristics and prognosis of young breast cancer patients with low expression of estrogen receptor

To evaluate the clinical characteristics and prognosis of young breast cancer patients with an ER of 1%–10%. Breast cancer patients aged ≤35 years old were selected and classified into three groups, ER-negative group, ER-low positive group (ER positivity: 1%–10%) and ER-high positive group (ER positivity: ≥10%), to compare their clinicopathological characteristics and prognosis. Of the 1387 patients assessed, 30.4% were ER-negative, 4.3% were ER-low positive, and 65.3% were ER-high positive. There was no difference in age, Tumor Node Metastasis (TNM) stage, histological type, adjuvant chemotherapy and adjuvant radiation therapy among the three groups (p > 0.05). A higher histological grade and greater Human Epidermal Growth Factor Receptor-2 (HER-2) positivity were observed in the ER-low positive group than in the ER-high positive group (p < 0.001). The number of patients with Progesterone Receptor (PR) negative in the ER-low positive group was between the other two groups. The recurrence rate of breast cancer in the ER-low positive group was 27.1%, which was similar to that of the ER-negative group (28%; p > 0.05) but higher than the ER-high positive group (21.4%; p = 0.03). After a median follow-up of 74 months, the ER-high positive group had the longest Disease Free Survival (DFS) compared with the ER-negative group (p < 0.0001) and ER-low positive group (p < 0.05), while there was no significant difference in DFS between the latter two groups (p = 0.73). Similarly, the ER-high positive group had the longest Overall Survival (OS) than the ER-negative group (p < 0.0001) and the ER-low positive group (p < 0.05), while there was no statistical difference in OS between the latter two groups (p = 0.77). After endocrine therapy, no improvement in DFS (p = 0.71) and OS (p = 0.54) was observed in the ER-low positive group. In young breast cancer patients, the clinicopathological characteristics of the ER-low positive group were different from the ER-high positive group but were more similar to the ER-negative group. The DFS and OS were shorter than the ER-high group, and despite receiving endocrine therapy, DFS and OS of the ER-low positive group were not significantly prolonged.

Outcomes in patients with non-invasive breast carcinoma.

Non-invasive breast carcinoma is considered to be localized disease and is distinguished from invasive ductal and lobular carcinomas. The local recurrence of non-invasive carcinoma after surgery may lead to development of invasive carcinoma and promote distant metastasis, which worsens the prognosis for breast cancer mortality. The distant metastasis of non-invasive carcinoma may involve the ductal microvasculature without invasion. The outcomes of non-invasive breast carcinoma were examined in this retrospective cohort study. Of 872 primary breast cancers diagnosed at a single center between May 2008 and March 2022, 93 (10.6%) were found to be non-invasive carcinomas and were examined in this study. The breast cancer recurrence and survival rates of patients with non-invasive carcinoma were analyzed retrospectively. The median follow-up period was 1891 (range, 5-4804) days. All patients underwent surgical treatment [mastectomy with sentinel lymph node biopsy (SLNB) and partial mastectomy with or without SLNB, tumorectomy, and microdochectomy]. Postoperatively, radiation therapy was administered to 73 (78.4%) of the patients and endocrine therapy was administered to 64 (81.0%) of 79 patients with hormone-receptor positivity. Of 26 patients who underwent partial mastectomy with SLNB, 24 (92.3%) showed isolated tumor cells in the SLNs on one-step nucleic acid amplification. Local recurrence was observed in three (0.3%) patients; no distant metastasis was observed. One patient died of a noncancerous disease. The overall survival rate was 98.0% and the breast cancer-specific survival rate was 100.0%. Non-invasive breast carcinoma, like invasive breast carcinoma, causes local recurrence, but has a good prognosis without distant metastasis. The clinical significance of isolated tumor cells in the SLNs as a systemic component of non-invasive breast carcinoma remains to be elucidated.

Disease-free survival does not differ according to fertility preservation technique for young women with breast cancer

To study whether fertility preservation strategies using ovarian stimulation or without using it impact long-term disease-free survival of patients with breast cancer. Retrospective bicentric cohort study. Two university hospitals. In this study, 740 women with breast cancer, aged 18-43 years, who received primary fertility preservation between 2013 and 2019 after a diagnosis of localized breast cancer were included. Overall, 328 patients underwent at least 1 ovarian stimulation cycle (STIM group) and 412 had a technique without hormonal administration (no STIM group). Disease-free survival and overall survival up to May 2021 were compared between the 2 groups by log-rank test. Cox proportional-hazard regression model was used for multivariable analyses. Out of the 740 women who underwent fertility preservation, follow-up data were available for 269 women in the STIM group (82%) and 330 (80%) in the no STIM group. Kaplan-Meier estimates of disease-free survival at 4 years were 87.9% (82.8%-92.2%) and 83.1% (78.4%-87.3%) in the STIM and no STIM groups, respectively. After adjustment on prognostic parameters, no significant difference in breast cancer recurrence rate was observed between the STIM and no STIM groups (hazard ratios, 0.83 [0.64-1.08]). Kaplan-Meier estimate of overall survival at 4 years was 97.6% (95.3%-99.2%) and 93.6% (90.9%-95.9%) in the STIM and no STIM groups, respectively. Overall survival was higher in the STIM group than no STIM group (log-rank test). After adjustment on prognostic parameters, the risk of death remained significantly lower in the STIM group (Hazard Ratio, 0.55 [0.35-0.85]). In our cohort, STIM for fertility preservation in breast cancer did not significantly impact disease-free survival but was associated with higher overall survival. The disease-free survival and overall survival of young patients with breast cancer were not impacted by fertility preservation techniques irrespective of the timing of chemotherapy (neoadjuvant or adjuvant) and the use of ovarian stimulation. Nevertheless, because death and recurrence were rare events, these results should be taken with caution.

Association of hormone receptor status with cardiovascular disease mortality in 399,209 patients with stage I to III breast cancer: A population-based study.

Adjuvant endocrine therapy (AET) is known to reduce the risk of hormone receptor-positive (HR+) breast cancer (BC) recurrence and mortality rates, but its impact on cardiovascular disease (CVD) events is unclear. The primary objective of this study was to analyze the association of HR status with CVD mortality in patients with stage I to III BC. A retrospective study of patients with stage I to III BC was conducted using the 2004 to 2016 Surveillance, Epidemiology, and End Results (SEER) database, and patients were grouped according to their HR status. Propensity score matching (PSM) was used to adjust for heterogeneity between the groups. The cumulative incidence rate of CVD mortality was evaluated via a cumulative incidence curve. Univariate and multivariate Fine and Gray's competing risk regression models were used to identify risk factors associated with CVD mortality. In total, 399,209 patients with BC were included in this study, and 329,958 patients (82.65%) were HR-positive. The cumulative incidence of CVD death was 8.28% in stage I to III BC patients. In the constituent ratio analysis, primary BC was the leading cause of death (45.29%, N = 31,465), followed by heart disease (16.07%, N = 11,166). Compared to the second year following BC diagnosis, the risk of CVD-specific death gradually increased. After PSM, 65,952 pairs of patients were matched, which led to the equilibrium of all variables between the HR-negative cohort and HR+ cohort. Multivariate analysis indicated that HR status was not significantly associated with the risk of CVD mortality, with a hazard ratio of 1.01 (P = .895). This study highlights the importance of understanding the associations between risk factors and CVD for BC patients. HR status was not associated with the risk of CVD mortality in this study.

Simultaneous Fat Grafting During Tissue Expander-to-Implant Exchange: A Propensity Score-Matched Analysis.

Implant-based breast reconstruction (IBBR) is the most common technique for breast reconstruction. The primary resource for correcting deformities, once patients have achieved an adequate volume with two-stage IBBR, is autologous fat grafting. We compared the surgical outcomes of simultaneous fat grafting during TE-to-implant exchange (SFG + TtIE) versus no fat grafting during TE-to-implant exchange (No-FGX). A retrospective review was performed of all consecutive patients undergoing two-stage implant-based breast reconstruction with TE from January 2011 to December 2020. Propensity score matching was implemented to optimize comparability. The control group did not receive fat grafting at the time of TE-to-implant exchange. After propensity score matching, 196 reconstructions were evaluated, 98 in each group. Reconstructions in the SFG + TtIE received larger implants during exchange in comparison with the No-FGX group (539 ± 135.1-cc versus 495.97 ± 148-cc, p=0.035). The mean volume of fat lipoinjected during TE-to-implant exchange in the SFG + TtIE group was 88.79 ± 41-ml. A higher proportion of reconstructions in the SFG + TtIE group underwent additional fat grafting after exchange versus the No-FGX group (19% versus 9%, p = 0.041). After propensity score matching, only the rate of fat necrosis after exchange was significantly higher in the SFG + TtIE group (10% versus 2%, p = 0.017). The rate of breast cancer recurrence (3% versus 5%, p = 1.00) was comparable between the groups. SFG + TtIE is a safe procedure to improve the envelope of reconstructed breasts during two-stage IBBR. SFG + TtIE does not increase the rate of periprosthetic infection or wound-related complication versus no fat grafting during TE-to-implant exchange, but increases the rate of fat necrosis. Therapeutic study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Comparison of Modified Radical Mastectomy with Breast Conservative Surgery in term of Recurrence of Breast Cancer

Objectives: To compare the modified radical mastectomy with breast conservative surgery in term of recurrence of breast cancer. Material and methods: Between April 2021 to October 2021, total 60 women having age 30 years to 60 years were selected from Department of Surgery, D.G Khan Hospital, D.G Kahn. Type of study was randomized controlled trial. Recurrence rate of breast cancer was compared between the both groups. Results: Mean age was 43.83 ± 9.633 years mean duration of breast cancer was 5.43 ± 1.890 years. Total 5 (16.67%) patients of MRM group found with recurrence while in conservative surgery group, it was found in 13 (43.33%) patients. Significantly (P = 0.047) higher proportion of recurrence was noted in conservative surgery group as compared to MRM group. Conclusion: Results of present study revealed that recurrence rate of breast cancer is significantly high after breast conservative surgery as compared to modified radical mastectomy. 3rd and 4th decade of life was common. Keywords: MRM, breast cancer, breast conservative surgery, recurrence

Breast cancer recurrence after immediate and delayed postmastectomy breast reconstruction-A systematic review and meta-analysis.

BackgroundOncological safety of different types and timings of PMBR after breast cancer remains controversial. Lack of stratified risk assessment in literature makes current clinical and shared decision‐making complex. This is the first systematic review and meta‐analysis to evaluate differences in oncological outcomes after immediate versus delayed postmastectomy breast reconstruction (PMBR) for autologous and implant‐based PMBR separately.MethodsA systematic literature search was performed in MEDLINE, Cochrane Library, and Embase. The Cochrane Collaboration Handbook and Meta‐analysis Of Observational Studies in Epidemiology checklist were followed for data abstraction. Variability in point estimates attributable to heterogeneity was assessed using I 2‐statistic. (Loco)regional breast cancer recurrence rates, distant metastasis rates, and overall breast cancer recurrence rates were pooled in generalized linear mixed models using random effects.ResultsFifty‐five studies, evaluating 14,217 patients, were included. When comparing immediate versus delayed autologous PMBR, weighted average proportions were: 0.03 (95% confidence interval [CI], 0.02–0.03) versus 0.02 (95% CI, 0.01–0.04), respectively, for local recurrences, 0.02 (95% CI, 0.01–0.03) versus 0.02 (95% CI, 0.01–0.03) for regional recurrences, and 0.04 (95% CI, 0.03–0.06) versus 0.01 (95% CI, 0.00–0.03) for locoregional recurrences. No statistically significant differences in weighted average proportions for local, regional and locoregional recurrence rates were observed between immediate and delayed autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrences after autologous PMBR, and of all outcome measures after implant‐based PMBR.ConclusionsDelayed autologous PMBR leads to similar (loco)regional breast cancer recurrence rates compared to immediate autologous PMBR. This study highlights the paucity of strong evidence on breast cancer recurrence after specific types and timings of PMBR.Lay summery Oncologic safety of different types and timings of postmastectomy breast reconstruction (PMBR) remains controversial.Lack of stratified risk assessment in literature makes clinical and shared decision‐making complex.This meta‐analysis showed that delayed autologous PMBR leads to similar (loco)regional recurrence rates as immediate autologous PMBR. Data did not allow comparing weighted average proportions of distant metastases and total breast cancer recurrence after autologous PMBR, and of all outcome measures after implant‐based PMBR.Based on current evidence, oncological concerns do not seem a valid reason to withhold patients from certain reconstructive timings or techniques, and patients should equally be offered all reconstructive options they technically qualify for.

Tumor-Targeted Injectable Double-Network Hydrogel for Prevention of Breast Cancer Recurrence and Wound Infection via Synergistic Photothermal and Brachytherapy.

The high locoregional recurrence rate and potential wound infection in breast cancer after surgery pose enormous risks to patient survival. In this study, a polyethylene glycol acrylate (PEGDA)‐alginate double‐network nanocomposite hydrogel (GPA) embedded with 125I‐labeled RGDY peptide‐modified gold nanorods (125I‐GNR‐RGDY) is fabricated. The double‐network hydrogel is formed by injection of GPA precursor solutions into the cavity of resected cancerous breasts of mice where gelation occurred rapidly. The enhanced temperature‐induced PEGDA polymerization driven by near‐infrared light irradiation, and then, the second polymer network is crosslinked between alginate and endogenous Ca2+ around the tumor. The double‐network hydrogel possesses a dense polymer network and tightly fixes 125I‐GNR‐RGDY, which exhibit superior persistent photothermal and radioactive effects. Hyperthermia induced by photothermal therapy can inhibit self‐repair of damaged DNA and promote blood circulation to improve the hypoxic microenvironment, which can synergistically enhance the therapeutic efficacy of brachytherapy and simultaneously eliminate pathogenic bacteria. Notably, this nanocomposite hydrogel facilitates antibacterial activity to prevent potential wound infection and is tracked by single‐photon emission computerized tomography imaging owing to isotope labeling of loaded 125I‐GNR‐RGDY. The combination of photothermal therapy and brachytherapy has enabled the possibility of proposing a novel postoperative adjuvant strategy for preventing tumor recurrence and wound infection.

Abstract 213: Assessing the role of X-ray radiation in combination with a DNA-PK inhibitor on cellular activity and adhesion using an in vitro HER2-positive breast cancer model

Abstract Introduction: Breast cancer (BC) is the most common cancer for women regardless of ethnicity, and the leading cause of cancer-related deaths in women. Radiation therapy (XRT) plays a vital role in multidisciplinary treatment approaches. Although XRT has been found to reduce breast cancer recurrence and mortality rate, like all other therapeutics, XRT contains some risks. Radiation can increase the mortality rate due to the risk of ischemic heart diseases. As part of an overall effort to understand the interaction between different types of radiations (e.g., radiopharmaceutical therapy (RPT) with β or α-particle emitters) and DNA double-strand break repair (DSB) repair pathways, we observed that impairment of DNA DSB by DNA-PKcs inhibitor (NU7441) fragmented HER2-positive BC spheroids in the presence of XRT. This could be possibly due to the modulation of cellular adhesion protein mediated by DNA-PK inhibition. In this study, we aim to assess the spheroids fragmentations and also measure the cell viability and levels of a cell adhesion protein, β1-integrin in irradiated HER2-positive monolayer cells, to get a mechanistic view for XRT and NU7441 combinatorial action so as to compare with β- or α-emitter RPT. Methods: In brief, NT2.5 BC spheroids were formed in agarose-coated 96-well plates. For both spheroids and monolayer cells, half of the media was replaced with fresh media containing 1 nM-5μM of NU7441 every other day. A colorimetric cell viability kit was used to measure cell viability and western blot analysis was performed to measure the β1-integrin level, which was normalized against β-actin. Results: Microscopic analysis suggested that XRT increased spheroid fragmentations in the presence of NU7441 compared to the XRT alone. Interaction between XRT and NU7441 (6.68% of the total variation, P<0.0001) was found for the cell viability data, where XRT (74.07% of the total variation, P<0.0001) and NU7441 (5.07% of the total variation, P<0.0001) both regulated cell viability on their own. Western blot data suggest that β1-integrin level was reduced for 8 Gy XRT and 5 μM NU7441 combination compared to the no XRT and vehicle combination. Moreover, 2-way ANOVA analysis revealed that XRT plays a role to regulate the β1-integrin level in NT2.5 monolayer cells (57.61% of the total variation, P<0.0001). Conclusion: XRT increased BC spheroids fragmentations when DNA damage was inhibited by a small molecule inhibitor. XRT and NU7441 both regulated NT2.5 cell viability with an interaction between them. Furthermore, XRT reduced β1-integrin level in monolayer NT2.5 cells. The XRT and NU7441 combination may induce fragmentations by decreasing cell viability and adhesion proteins. Future studies assessing the mechanisms of XRT and DNA PK inhibitor in BC spheroids and in vivo are warranted to confirm these results. Citation Format: Mahmud Hasan, Ioanna Liatsou, George Sgouros. Assessing the role of X-ray radiation in combination with a DNA-PK inhibitor on cellular activity and adhesion using an in vitro HER2-positive breast cancer model [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 213.

Breast cancer recurrence and survival rates in patients who underwent breast-conserving surgery under non-mechanically ventilated anesthesia.

Recurrence after primary treatment is an important obstacle to the curing of primary breast cancer. Less-immunosuppressive anesthetic techniques, such as local anesthesia with lidocaine, intravenous anesthesia (IVA) with propofol, and/or sedation with midazolam under spontaneous breathing may reduce breast cancer recurrence compared with standard general anesthesia techniques such as IVA and inhalation anesthesia with opioids under mechanical ventilation. The aim of this study was to analyze the factors involved in breast cancer recurrence in patients who underwent breast-conserving surgery (BCS) under non-mechanically ventilated anesthesia. The study included 491 consecutive patients with stages 0-III breast cancer who underwent BCS/axillary lymph-node management with local anesthesia and IVA and/or sedation under non-mechanical ventilation between May 2008 and September 2021. Survival and recurrence were assessed by retrospective cohort analysis. The median follow-up period was 2565 days (range, 28-4834 days). The overall and breast cancer-specific survival rates were 92.9% and 95.6%, respectively. Twenty-one deaths, of which 11 were breast cancer-related, occurred. Disease recurred in 29 (5.9%) patients, of whom 15 patients received neoadjuvant chemotherapy (NAC) and 14 patients received adjuvant therapy (chemotherapy in 12 cases). The surgical procedure performed, but not other clinicopathological factors [recurrence site, P stage, tumor subtype, and disease-free interval (DFI)], differed between the NAC and adjuvant therapy groups. The DFI tended to be shorter in the NAC group than in the adjuvant therapy group. The pathological therapeutic effect grade after NAC was 1 in 12 patients and ≥2 in 3 patients. More than 50% (15/29) of patients with recurrence who underwent BCS were given NAC, but most patients did not respond to it. Similarly, adjuvant chemotherapy may not have contributed to the eradication of residual tumor cells after BCS. To reduce breast cancer recurrence in patients undergoing BCS, treatment strategies, especially for patients who do not respond to NAC or adjuvant chemotherapy, need to be developed. Non-mechanical ventilation anesthesia may also affect the incidence of breast cancer recurrence.

Bio-Imaging-Based Machine Learning Algorithm for Breast Cancer Detection.

Breast cancer is one of the most widespread diseases in women worldwide. It leads to the second-largest mortality rate in women, especially in European countries. It occurs when malignant lumps that are cancerous start to grow in the breast cells. Accurate and early diagnosis can help in increasing survival rates against this disease. A computer-aided detection (CAD) system is necessary for radiologists to differentiate between normal and abnormal cell growth. This research consists of two parts; the first part involves a brief overview of the different image modalities, using a wide range of research databases to source information such as ultrasound, histography, and mammography to access various publications. The second part evaluates different machine learning techniques used to estimate breast cancer recurrence rates. The first step is to perform preprocessing, including eliminating missing values, data noise, and transformation. The dataset is divided as follows: 60% of the dataset is used for training, and the rest, 40%, is used for testing. We focus on minimizing type one false-positive rate (FPR) and type two false-negative rate (FNR) errors to improve accuracy and sensitivity. Our proposed model uses machine learning techniques such as support vector machine (SVM), logistic regression (LR), and K-nearest neighbor (KNN) to achieve better accuracy in breast cancer classification. Furthermore, we attain the highest accuracy of 97.7% with 0.01 FPR, 0.03 FNR, and an area under the ROC curve (AUC) score of 0.99. The results show that our proposed model successfully classifies breast tumors while overcoming previous research limitations. Finally, we summarize the paper with the future trends and challenges of the classification and segmentation in breast cancer detection.

PC20. LONG-TERM CANCER RECURRENCE RATES FOLLOWING NIPPLE-SPARING MASTECTOMY: A 10-YEAR FOLLOW UP STUDY

PURPOSE: Although nipple-sparing mastectomy (NSM) is a widely accepted and popular technique, limited data exists examining long-term cancer recurrence rates associated with it. This study sought to analyze rates of breast cancer recurrence in patients who underwent therapeutic NSM with a median of 10 years of follow-up. METHODS: A single institution retrospective review identified all patients who underwent NSM with a median of 10-years of follow-up. Analysis focused on patient demographics, mastectomy specimen pathology, and oncologic outcomes including cancer recurrence. Independent risk factors for locoregional recurrence were assessed via univariate logistic regression. RESULTS: 158 therapeutic NSMs were performed on 152 patients. Invasive ductal carcinoma (48.7%) and ductal carcinoma in situ (35.4%) were the most common tumor types seen on pathology. Multifocal/multicentric disease and lymphovascular invasion were present in 34.1% and 12.8% of specimens, respectively. Sentinel lymph node biopsy rate was 82.9%, with 15.2% reported as positive. Rates of positive frozen and permanent subareolar biopsy were 5.4% and 8.3%, respectively. Low cancer stages were overwhelmingly more common, with stage I and stage 0 representing 40.5% and 35.4% of the population, respectively. Incidence of recurrent disease was 3.2% per mastectomy and 3.3% per patient. Univariate analysis did not identify any variables that were independent risk factors for locoregional recurrence. CONCLUSION: At a median of 10 years of follow-up, overall cancer recurrence rates are low in patients who undergo NSM, further suggesting the safety of this technique. Regardless, close surveillance should remain a goal to ensure prompt detection of any sign of recurrence.

Aromatase inhibitors versus tamoxifen in premenopausal women with oestrogen receptor-positive early-stage breast cancer treated with ovarian suppression: a patient-level meta-analysis of 7030 women from four randomised trials.

SummaryBackgroundFor women with early-stage oestrogen receptor (ER)-positive breast cancer, adjuvant tamoxifen reduces 15-year breast cancer mortality by a third. Aromatase inhibitors are more effective than tamoxifen in postmenopausal women but are ineffective in premenopausal women when used without ovarian suppression. We aimed to investigate whether premenopausal women treated with ovarian suppression benefit from aromatase inhibitors.MethodsWe did a meta-analysis of individual patient data from randomised trials comparing aromatase inhibitors (anastrozole, exemestane, or letrozole) versus tamoxifen for 3 or 5 years in premenopausal women with ER-positive breast cancer receiving ovarian suppression (goserelin or triptorelin) or ablation. We collected data on baseline characteristics, dates and sites of any breast cancer recurrence or second primary cancer, and dates and causes of death. Primary outcomes were breast cancer recurrence (distant, locoregional, or contralateral), breast cancer mortality, death without recurrence, and all-cause mortality. As distant recurrence invariably results in death from breast cancer several years after the occurrence, whereas locoregional recurrence and new contralateral breast cancer are not usually fatal, the distant recurrence analysis is shown separately. Standard intention-to-treat log-rank analyses estimated first-event rate ratios (RR) and their confidence intervals (CIs).FindingsWe obtained data from all four identified trials (ABCSG XII, SOFT, TEXT, and HOBOE trials), which included 7030 women with ER-positive tumours enrolled between June 17, 1999, and Aug 4, 2015. Median follow-up was 8·0 years (IQR 6·1–9·3). The rate of breast cancer recurrence was lower for women allocated to an aromatase inhibitor than for women assigned to tamoxifen (RR 0·79, 95% CI 0·69–0·90, p=0·0005). The main benefit was seen in years 0–4 (RR 0·68, 99% CI 0·55–0·85; p<0·0001), the period when treatments differed, with a 3·2% (95% CI 1·8–4·5) absolute reduction in 5-year recurrence risk (6·9% vs 10·1%). There was no further benefit, or loss of benefit, in years 5–9 (RR 0·98, 99% CI 0·73–1·33, p=0·89) or beyond year 10. Distant recurrence was reduced with aromatase inhibitor (RR 0·83, 95% CI 0·71–0·97; p=0·018). No significant differences were observed between treatments for breast cancer mortality (RR 1·01, 95% CI 0·82–1·24; p=0·94), death without recurrence (1·30, 0·75–2·25; p=0·34), or all-cause mortality (1·04, 0·86–1·27; p=0·68). There were more bone fractures with aromatase inhibitor than with tamoxifen (227 [6·4%] of 3528 women allocated to an aromatase inhibitor vs 180 [5·1%] of 3502 women allocated to tamoxifen; RR 1·27 [95% CI 1·04–1·54]; p=0·017). Non-breast cancer deaths (30 [0·9%] vs 24 [0·7%]; 1·30 [0·75–2·25]; p=0·36) and endometrial cancer (seven [0·2%] vs 15 [0·3%]; 0·52 [0·22–1·23]; p=0·14) were rare.InterpretationUsing an aromatase inhibitor rather than tamoxifen in premenopausal women receiving ovarian suppression reduces the risk of breast cancer recurrence. Longer follow-up is needed to assess any impact on breast cancer mortality.FundingCancer Research UK, UK Medical Research Council.

Assessment of Suspected Breast Lesions in Early-Stage Triple-Negative Breast Cancer during Follow-Up after Breast-Conserving Surgery Using Multiparametric MRI.

Background The local recurrence rate of triple-negative breast cancer (TNBC) can be as high as 12%.The standard treatment for early-stage TNBC is breast-conserving surgery (BCS), followed by postoperative radiotherapy with or without chemotherapy. However, detection of the local recurrence of the disease after radiotherapy is a major issue. Objective The aim of this study was at investigating the role of dynamic and functional magnetic resonance imaging (MRI) during follow-up after BCS and radiotherapy with/without chemotherapy to differentiate between locoregional recurrence and postoperative fibrosis. Patients and Methods. This prospective study was conducted at the oncology, radiology, and pathology departments, Tanta University. It involved 50 patients with early-stage TNBC who were treated with BCS, followed by radiotherapy with/without chemotherapy. The suspected lesions were evaluated during the follow-up period by sonomammography. All patients were subjected to MRI, including conventional sequences, diffusion-weighted imaging (DWI), and dynamic postcontrast study. Results Ten cases were confirmed as recurrent malignant lesions. After contrast administration, they all exhibited irregular T1 hypodense lesions of variable morphology with diffusion restriction and positive enhancement. Eight cases displayed a type III curve, while two showed a type II curve. Histopathological assessment was consistent with the MRI findings in all eight cases. The combination of the data produced by DWI-MRI and dynamic contrast-enhanced (DCE) MRI resulted in 100%sensitivity, 92.5% specificity, 90.9% positive predictive value, 100% negative predictive value, and 98% accuracy. Conclusion Combination of DWI-MRI and DCE-MRI could have high diagnostic value for evaluating postoperative changes in patients with TNBC after BCS, followed by radiotherapy with/without chemotherapy. Trial Registrations. No trial to be registered.