Breast Cancer Recurrence Rates Research Articles

Real-World Comparative Analysis of Trastuzumab Originator and Biosimilars: Safety, Efficacy, and Cost Effectiveness.

Despite the global use of trastuzumab biosimilars, concerns remain regarding their efficacy and safety. In particular, when used concurrently with pertuzumab, trastuzumab biosimilars lack extensive real-world data and safety information. Additionally, as cancer drug expenditures continue to rise worldwide, cost savings from biosimilars have become increasingly important. This study aims to assess the safety, efficacy, and cost effectiveness of trastuzumab originators and their biosimilars in real-world clinical settings, focusing on a large patient population. The analysis included 31,661 patients with HER2-positive breast cancer from the Medical Data Vision Co., Ltd. database in Japan. Additionally, adverse event reports for the trastuzumab originator and its biosimilars were obtained for 58,799 patients from the World Health Organization's VigiBase, the global adverse event reporting database. No significant differences were observed in heart failure hospitalizations, liver dysfunction, or infusion reaction rates in both the Medical Data Vision Co., Ltd. database and the World Health Organization's VigiBase. In the Medical Data Vision Co., Ltd. database, the addition of pertuzumab did not significantly influence the incidence of adverse events, and the use of biosimilars significantly reduced medical costs, with no significant difference in breast cancer recurrence rates. By analyzing two large and diverse datasets from multiple perspectives, we obtained reliable results that the trastuzumab originator and its biosimilars have similar safety profiles. The concurrent use of pertuzumab was also found to be safe. The use of biosimilars can lead to cost savings. These findings provide crucial insights for the evaluation and adoption of biosimilars in clinical practice.

Abstract B156: Exploring identity-specific stressors among Black women with a family history of cancer

Abstract Background: Compared to women of other racial/ethnic groups, Black women are more likely to be diagnosed with aggressive subtypes of breast cancer (including triple-negative breast cancer), diagnosed at younger ages, diagnosed at more advanced stages, and have higher mortality rates and poorer survival outcomes. Black women also experience higher rates of breast cancer recurrence, which further exacerbates the survival disparities. These disparities are influenced by a complex interplay of genetic, environmental, and social factors, including chronic stress and discrimination. Understanding identity-specific stressors will help identify potential risk factors impacting breast cancer outcomes among Black women.Objective: This study aims to identify common stressors among Black women aged 18 to 49 with a family history of cancer, exploring potential links to breast health risk. Methods: We conducted a grounded theory study, including qualitative interviews from Black women in the Augusta, Georgia, area (N=47) discussing life as a Black woman and sources of stress. Participants with a close family history of cancer (defined as having at least one first- or second-degree relative diagnosed with cancer) were selected for this analysis (n=22). We applied the Sort & Sift, Think & Shift method for analysis. Results: We identified three categories in response to the research question, including healthcare access barriers and medical invalidation (particularly in rural communities), intergenerational trauma, and Strong Black Woman persona (characterized by independence, emotional suppression, and a tendency to care for others while neglecting their own needs). Participants described these categories in reference to themselves and their female family members with cancer. Participants reported stress related to jobs and caregiving responsibilities, lack of adequate social support, lack of time and finances necessary for self-care, and racial discrimination in medical settings. Conclusion: The identified stressors highlight the complex interplay between familial cancer history and daily stress experiences among Black women. These findings suggest the need for targeted interventions to mitigate stress and potentially reduce breast cancer risk. Further research is warranted to explore these themes in relation to breast cancer outcomes. Citation Format: Samantha R. Jones, Debbynie Barsh, Kathleen McIntyre, Christy J.W. Ledford. Exploring identity-specific stressors among Black women with a family history of cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B156.

Study of Survival, Metastasis and Recurrence Rate of Breast Cancer in Comparison With Different Regimens of Endocrine Therapy

Study of Survival, Metastasis and Recurrence Rate of Breast Cancer in Comparison With Different Regimens of Endocrine Therapy

Reviewing the recurrence rates in stage I-III HR or ER positive breast cancer in obese patients given multi-modal weight loss plan post-treatment with aromatase inhibitors.

15 Background: Aromatase inhibitors (AIs) in the treatment of endocrine recepter positive breast cancer stages I-III, poses significant challenges in the management of obesity. Obesity is not only associated with an increased risk of breast cancer incidence but also with higher rates of cancer recurrence and poorer treatment outcomes. Moreover, the use of AIs, while effective in reducing estrogen levels and preventing ER or HR positive breast cancer recurrence, may exacerbate weight gain and metabolic disturbances in obese individuals. Weight management strategies have experienced increased attention in breast cancer survivors in recent years, especially overweight or obese individuals. Novel data makes it possible to infer that obesity management activities and multimodal programs that incorporate dietary counseling and physical activity can reduce recurrence rates. Methods: Participants in this study were individuals with Stage I-III endocrine receptor positive breast cancer who had completed adjuvant therapy and had a BMI in the 40s or 50s, increasing risk of recurrence. Eligible patients were identified based on the start date for endocrine therapy. High-risk patients were then assigned to either the intervention or control group. Those in the intervention group received access to a dietician, along with informational pamphlets on physiology and weight loss strategies. Additionally, they were offered discounts to certain gyms or provided free access to fitness facilities. Both intervention and control groups were briefed about the study, with those in the intervention group encouraged to utilize the provided resources for weight management. Results: The evidence from our study will underscore the potential benefits of multimodal weight loss interventions in overweight or obese breast cancer survivors, particularly in improving anthropometric outcomes and enhancing overall quality of life. Conclusions: While the studies included in our analysis demonstrated reductions in body weight, BMI, and waist circumference, as well as improvements in quality of life measures, there remains a notable gap in understanding the impact of these interventions on breast cancer recurrence rates, especially in the context of endocrine-positive breast cancer treated with Aromatase Inhibitors (AIs).

Use of tamoxifene-controlled ovarian hyperstimulation for fertility preservation before breast cancer treatment: A prospective cohort study with a 5-year follow-up

PurposeFertility issues are of great concern for young women undergoing treatment for breast cancer (BC). Fertility preservation (FP) protocols using controlled ovarian stimulation (COS) with letrozole have been widely used with overall good results. However, letrozole cannot be used in every country in this context. This study aimed to assess the efficacy of tamoxifen for COS in women with early BC undergoing FP. MethodsThis multicentric prospective study included patients aged 18–40, diagnosed with stage I, II and III invasive BC, undergoing tamoxifen-COS before adjuvant or neoadjuvant chemotherapy (NAC). The primary endpoint was the efficacy of tamoxifen-COS protocol evaluated by the number of oocytes collected and vitrified. Secondary endpoints included the time interval before chemotherapy, breast cancer (BC) recurrence rates, and reproductive outcomes. ResultsNinety-five patients were included between 2014 and 2017, aged 31.5 ± 4 years on average. 37.9 % received NAC and 62.1 % received adjuvant chemotherapy. FP procedure was successful in 89.5 % of the cycles. The mean number of collected and vitrified oocytes was 12.8 ± 7.9 and 9.8 ± 6.2, respectively. The mean duration of COS was 10.4 ± 1.9 days. Median time before chemotherapy initiation was 3.6 weeks (IQR 3.1; 4.1) for women receiving NAC. Five-year relapse-free and overall survival rates were in-line with those expected in this population. Twenty-one women had spontaneous full-term pregnancies, while 5 underwent IVF cycles with frozen-thawed oocytes, without pregnancy. ConclusionTamoxifen-COS protocols appear to be feasible before adjuvant or NAC treatment in young BC patients and efficient in terms of oocyte yield.

P-317 Risk of endometrial polyps and hyperplasia after tamoxifen treatment in women with breast cancer: a population-based study in Taiwan

Abstract Study question This study aimed to examine the association between tamoxifen treatment and incident risks of uterine disease among breast cancer patients in Taiwan. Summary answer We found tamoxifen treatment group may have greater risk of endometrial polyps and hyperplasia than unexposured group after adjusting for age and body mass index. What is known already In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) breast cancer treatment trail reported that the women continue tamoxifen up to 10 years, compared with 5 years may reduce breast cancer recurrence and mortality rate. However, tamoxifen use has been reported to be associated with the cumulative risk of subsequently endometrial cancer during 5–14 years was 3.1%. Specifically, several Western studies have showed that the high incidence of endometrial cancer in breast cancer survivors with tamoxifen treatment. Study design, size, duration We conducted a retrospective cohort study using population-based data from Taiwan Cancer Registry and the National Health Insurance Research Database (NHIRD), and the National Population Registry Data set from 2011 to 2020. Participants/materials, setting, methods A total 138,934 newly diagnosed breast cancer female patients with age greater than 18 years old were included. We further used a 1-to-1 propensity score matching to generate comparable exposure and un-exposure groups. Cox proportional hazard regression models were used to examine the research question. All statistical analysis was performed using SAS version 9.4, and p-values < 0.05 were considered statistically significant Main results and the role of chance Incidence rate ratio (IRR) to compare incidence rate of uterine disease between tamoxifen treatment groups and unexposed group, adjusting for age and BMI. Our results showed that IRR were 1.36, 0.33, 3.73, 0.63, endometrial polyps, endometrial carcinoma, endometrial hyperplasia and uterine carcinosarcoma, respectively. This study found possible correlations between tamoxifen exposure with endometrial polyps and hyperplasia among breast cancer. During the 10-year study period, tamoxifen group did not significantly increase the risk of endometrial cancer in breast cancer survivors at aged 40 and over. Limitations, reasons for caution Our cohort study with 10-year period is its short study period, Tamoxifen group did not significantly increase the risk of endometrial cancer. Wider implications of the findings This cohort study found higher endometrial polyps and hyperplasia incidence rates among women with breast cancer who received tamoxifen women than those not treated with tamoxifen. Results of this study suggest that clinicians should consider the risk of uterine disease among tamoxifen use and counsel patients accordingly. Trial registration number KMUHIRB-G(II)20200217

Breast cancer recurrence rate after mastectomy in young females.

e12591 Background: Breast cancer is the most commonly diagnosed female cancer worldwide and the most common cause of cancer mortality in women. Surgical treatment of early breast cancer includes lumpectomy or mastectomy with or without reconstruction. Despite the surgeon’s best effort to perform a radical resection of the breast tissue during mastectomy to achieve locoregional control, residual fibroglandular tissue was found in 20% of breasts on postoperative breast MRI, which carries a risk of recurrence. Younger women with breast cancer have inferior survival rates despite receiving more aggressive therapy. Tumors in young women are more likely to be poorly differentiated, hormone receptor-negative, have a high proliferation index, and more lymphovascular invasion, which is partially explained by patients’ genetic profile. Another factor that could contribute to poor outcomes is the advanced stage at the time of diagnosis, including larger tumor size and higher rates of axillary lymph node positivity. This knowledge has motivated us to conduct this study that is dedicated to looking at the recurrence rate in young females following mastectomy. Methods: This is a retrospective study that collected data from young female patients who were diagnosed with breast cancer between January 2010 and August 2018, had an age at diagnosis of 18-45 years old, and underwent unilateral or bilateral mastectomy with or without reconstruction. The study also looked at the patient’s risk factors and genetic profile. Results: A total of 115 patients were diagnosed with early-stage breast cancer between January 2010 and August 2018 and underwent mastectomy. 81.74% were Caucasian females, and 8.7% were African American females. The mean age of diagnosis was 36.9 years. The mean BMI was 30.5 kg/m2. 59.13% of patients had a family history of breast cancer. The most common genetic mutations were BRCA1 at 7.83% and BRCA2 at 8.7%. 71% of patients underwent a bilateral mastectomy. 76% of patients had reconstruction. 77% of tumors were ER-positive, 68% PR-positive, and 26% HER2-positive. 49.4% of tumors were Nottingham grade 3. 52% of patients had no nodal involvement, while 35% had N1 disease. 34.6% had lymphovascular invasion. We found that 18/115 patients had recurrence of breast cancer following mastectomy. 5/17 patients had locoregional recurrence, while 12/17 patients had a distant recurrence; 1 patient’s recurrence data was unavailable. The median time to recurrence was 1147.5 days (335 to 3107). The 5-year recurrence free survival rate is 86% ± 3%. Conclusions: Our study found that 15.65% of young females had recurrence after mastectomy. To our knowledge, this is the first dedicated study to look at the recurrence rate after mastectomy in this young, high-risk patient population. Our study aims to encourage larger studies in young females with breast cancer to help tailor the treatment plan in this population.

Impact of semaglutide and tirzepatide administration on weight in women with stage I-III breast cancer.

e24140 Background: Weight gain and obesity are significant problems for women receiving adjuvant therapy for breast cancer and obesity is associated with adverse breast cancer outcomes. In addition, obesity is associated with negative impact on overall physical and mental health. The GLP-1 agonists, semaglutide (S) and tirzepatide (T), are effective in achieving weight loss and have been associated with decreased incidence of diabetes, stroke and overall mortality in the non-diabetic as well as diabetic populations. There are limited data on the efficacy and safety of GLP1 agonists in women with breast cancer. Methods: We performed a retrospective analysis of the association of S and T use with weight loss in patients with stage I-III breast cancer diagnosed and treated at the Yale Cancer Center/Yale New Haven Health Network between 2017 and 2022. After institutional review board approval, a database including 7149 patients including 92,989 office visits was constructed. Maximal weight loss after S/T prescription as well as mean weight loss were calculated. S and T treated patient’s stage distribution and rates of recurrence were compared to untreated patients. For patients without metastatic disease, repeated measures regression analysis was utilized to evaluate changes in weight and BMI. Results: Of the 5430 evaluable patients with non-metastatic disease, 70 (1.3%) were prescribed S or T. Mean age was 58 (41-78). 74% received endocrine therapy. Mean pretreatment weight was 95.8 kg and BMI was 35.9 kg/m2. Mean weight loss for S/T treated patients was 3.03 kg (3.9-2.13, p < .0001) corresponding to reduction in BMI of 1.1 kg/m2 (0.7-1.5 p < .0001). We also calculated maximal weight loss after S/T prescription. Mean maximal weight loss was 8.89 kg (6.71-10.98 P < .0001) corresponding to a mean maximal reduction in BMI of 3.2 kg/m2 (2.3-4.2 P < .0001). Rates of local, locoregional, and distant breast cancer recurrence were 1.5%, 0%, 1.5% in the S/T treated patients and 1.3%, 4.7% and 3.3% in the untreated patients. None of these differences were statistically significant. Conclusions: In this retrospective analysis, GLP-1 agonist are associated with clinically meaningful weight loss in overweight and obese women with early breast cancer. Recurrence risk did not appear to be preliminarily impacted by treatment. Additional research is needed on long term safety as well as weight loss maintenance with these drugs in breast cancer survivors.

A pilot study evaluating exercise intervention and body composition changes in patients with breast cancer and survivors.

e12527 Background: In breast cancer patients and survivors, higher weight and adipose tissue levels have been associated with cardiovascular disease, diabetes, osteoporosis, and cancer recurrence. Additionally, various breast cancer treatments can increase body weight, adipose tissue, and inflammatory markers, raising multiple health concerns for breast cancer patients. Recent studies have found exercise programs alongside breast cancer treatment decreased adipose tissue; however, the weight loss and lifestyle results were not maintained following the exercise program. It remains unclear what strategies are effective in implementing long term lifestyle changes. Methods: In this pilot study, breast cancer patients and survivors (N=24, individual=12, group=12) followed an exercise program for 6 months, followed by 6 months of follow up. Participants ranged from ages 36 to75. Participants were randomized into group and individual exercise sections. Anthropometric measurements were taken at baseline, 3 months and 1 year. One-year measures were used to indicate continued lifestyle changes. Results: Significant differences in fat % body composition were found between baseline and 3 months in both group and individual with an average change of 1.12% (5.9% max) and 1.32% (5.4% max) respectively (P=0.0090). In addition, the baseline and 1-year average change of both group 2.8% (8.8% max) and individual 1.5% (9.6% max) sections was also seen and statistically significant (P=0.0040). Patients in individual and group exercise sections had up to 9.6% and 8.8% decrease in adipose tissue over 1 year, respectively.However, no significant difference was found between the individual and group exercise sections (P=0.3244). Conclusions: Patients from both the individual and group exercise sections continued to decrease adipose tissue composition throughout the 1-year study period, including after formal exercise course cessation at 6 months. This indicates that both group and individual exercise courses may offer similar health benefits to breast cancer survivors. We are continuing long term data collection to evaluate sustainability of the intervention benefits and to monitor breast cancer recurrence rates. Clinical trial information: NCT04013568 . [Table: see text]

Abstract GS02-08: Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer

Abstract Background: Multiple studies have shown a low risk of ipsilateral breast events (IBE) or other recurrences for selected patients age 65-70 or older with Stage I breast cancers treated with breast conserving surgery (BCS) and endocrine therapy (ET) without adjuvant radiotherapy (RT). We designed a prospective single-arm trial, IDEA (Individualized Decisions for Endocrine therapy Alone), to see if younger postmenopausal patients could also be successfully treated without RT, adding a genomic assay to classic selection factors. Methods: Postmenopausal patients aged 50-69 with pT1N0 unifocal invasive breast cancer with margins 2 mm or wider after BCS whose tumors were ER+, PR+, and Her2- with Oncotype DX 21-gene recurrence score (RS) 18 or lower were eligible to avoid RT if they consented to take at least 5 years of ET and surveillance on study. The primary endpoint was the rate of breast cancer recurrence at 5 years of follow-up after BCS. A valid 5–year assessment was defined as a clinical assessment within 4 months prior to the 5-year anniversary or later. Follow-up time was calculated from the date of BCS until first recurrence [ipsilateral breast events (IBE) or regional or distant failures] or to last clinical follow-up. The time-to-event endpoint was calculated using the product-limit method of Kaplan and Meier measured from the date of BCS. Results: 200 eligible patients were enrolled from 13 US institutions between June 2015 and October 2018. Median age was 63 years (IQR 58-66); mean RS was 11.2 (SD 4.8). Tumors were grade 1 in 85 patients, grade 2 in 109, and grade 3 in 6. Mean tumor size was 10 mm (SD 4.6). Lymphovascular invasion was present in 16 tumors and an extensive intraductal component in 11. Median follow-up time was 5.21 years (IQR 5.01-5.97); 8 of 14 patients with less than 56 months of follow-up were lost to follow-up. Overall and breast cancer-specific survival rates at 5 years were both 100%; 2 deaths occurred later than 5 years. The 5-year freedom from recurrence was 99% (95% CI, 96%-100%). One of the two events occurring by 5 years was an isolated axillary recurrence at 21 months treated with axillary dissection and breast and regional nodal irradiation. The other was an IBE at 49 months, treated with repeat BCS. Both these patients had been compliant with ET. Six additional patients recurred later than 5 years after BCS (5 IBEs, 1 IBE plus regional recurrence). Crude rates of IBE for the entire follow-up period for patients aged 50-59 and 60-69 were 3.3% (2/60) and 3.6% (5/140), respectively; crude rates of overall relapse were 5.0% (3/60) and 3.6% (5/140). Conclusions: This multicenter trial of ET without RT following BCS achieved a very low risk of relapse for postmenopausal patients with Stage I cancers using a genomic assay in combination with classic clinical and biologic features for treatment selection, including for patients younger than age 60. IDEA demonstrates a 5-year probability of recurrence consistent with or lower than the 4% risk estimated a priori, and the patients accrued were younger when compared to prior prospective trials (e.g., PRIME II, minimum age 65; CALGB 9343, minimum age 70; LUMINA, median age 67). The results of ongoing NRG BR007 trial, which randomly allocates women meeting these eligibility criteria to receive RT or not, and similar randomized and single-arm studies will help determine whether the option of avoiding initial RT can be offered to a broader group of women than current guidelines recommend. Long-term follow-up beyond the 5-year required period of ET will be important to determine if the risk of recurrence increases, particularly after discontinuation of ET. Citation Format: Reshma Jagsi, Kent Griffith, Eleanor Harris, Jean Wright, Abram Recht, Alphonse Taghian, Lucille Lee, Meena Moran, William Small, Candice Johnstone, Asal Rahimi, Gary Freedman, Mahvish Muzaffar, Bruce Haffty, Kathleen Horst, Simon Powell, Jody Sharp, Michael Sabel, Anne Schott, Mahmoud El-Tamer. Five-year outcomes of the IDEA trial of endocrine therapy without radiotherapy after breast-conserving surgery for postmenopausal patients age 50-69 with genomically-selected favorable Stage I breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS02-08.

Abstract PO5-23-05: The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for Breast Cancer

Abstract Introduction: Breast conserving surgery (BCS) represents the preferred option for surgical treatment for a majority of patients with early-stage breast cancer who are eligible for this approach. When compared with mastectomy approaches, BCS provides patients with equivalent survival while preserving the affected breast. It is necessary to achieve clear surgical margins as positive lumpectomy margins are associated with an increased risk for ipsilateral breast tumor recurrence. With advances in imaging techniques, as well as effective systemic therapy and contemporary radiation therapy, local recurrence after BCS has decreased and overall survival for patients has improved. Retrospective studies have quantified the recurrence rate in unifocal breast cancer as 8 - 15% at 20 years. The NCCN recommends annual mammography at least 6 months after post-lumpectomy radiation therapy, but there is little data regarding more frequent surveillance after lumpectomy in the early post-operative setting. The purpose of this study was to evaluate the impact of short interval surveillance mammography on the detection of early in-breast recurrence in patients undergoing BCS. Methods: Our IRB-approved Breast Cancer Database was queried for patients enrolled from 11/2009 to 6/2023 who underwent breast conservation surgery for a diagnosis of in situ or invasive breast cancer in this retrospective analysis. Per our institutional protocol, patients were recommended to undergo diagnostic mammography of the treated breast(s) every 6 months for 2 years after BCS. After the initial 2 year period, bilateral mammography was performed annually in the absence of other indications. Additional supplemental imaging such as breast ultrasound and MRI were performed at physician discretion and based on patient risk and breast density. Variables of interest included the presence of pathogenic germline mutations, family history of breast cancer, and disease characteristics. Our primary endpoint was ipsilateral breast tumor recurrence. Results: Of 2491 patients who underwent breast conservation surgery for in situ or invasive breast cancer, 191 (7.7%) developed recurrent disease, including ipsilateral and contralateral recurrence, and distant disease, in the study period. A total of 83 (3.2%) patients developed ipsilateral breast recurrence during the entire study period. Of those, 19 (22.9%) were detected within the first two years after surgery. Six of the 19 patients (31.6%) had their recurrences detected on yearly diagnostic mammography while 6 (31.6%) patients had their recurrences detected on interval 6-month unilateral diagnostic imaging. In both groups, 5/6 recurrences were invasive disease after an original diagnosis of invasive cancer, and the remaining patient had recurrent DCIS. The remaining 7/19 patients (36.8%) had their ipsilateral recurrences detected on palpation or other diagnostic imaging. In this group as well, there was one case of recurrent DCIS, with the remaining 6 cases representing recurrent invasive cancer. Of the 19 patients with ipsilateral recurrences, none had pathogenic germline mutations. 4 of the 19 patients (21%) had positive margins after their initial lumpectomy surgery with re- excisions required to achieve clear margins. Conclusion: Interval diagnostic surveillance imaging every 6 months after breast conserving surgery identified almost one-third of the ipsilateral breast tumor recurrences that occurred within the first 2 years after surgery in our population. While our numbers are small, the relationship of re-excision lumpectomy surgery to subsequent risk for local recurrence has been described by others, and bears further study. Particularly in view of our observation that the majority of in-breast recurrences were invasive, our data supports the practice of more frequent imaging follow up in the first 2 years after breast conserving surgery. Citation Format: Pabel Miah, Laura Fiedler, Anthony Baez, Athanasios Sevdalis, Alyssa Marmer, Charles DiMaggio, Linda Pak, Richard Shapiro, Karen Hiotis, Deborah Axelrod, Amber Guth, Freya Schnabel. The Impact of Bi-Annual Diagnostic Imaging on Detecting Ipsilateral Breast Recurrence in Patients Undergoing Breast Conserving Surgery for Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-23-05.

Abstract PO5-11-08: Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer

Abstract Background: Treatment with endocrine therapy such as tamoxifen has been identified as one of the most important variables linked with survival among women with hormone receptor-positive breast cancer (BC). There is significant risk reduction of BC recurrence and BC mortality at 15 years among patients treated with tamoxifen for 5 years compared to no endocrine therapy. Tamoxifen is metabolized in the liver via multiple cytochrome P (CYP) isoforms. To ensure optimal efficacy of tamoxifen, consideration must be given to concomitant use of other commonly prescribed drugs such as antidepressants. Some selective serotonin reuptake inhibitors (SSRIs) are potent inhibitors of CYP2D6, an enzyme that metabolizes tamoxifen into its active metabolite, endoxifen, which has anti-tumor effect. Such inhibition can reduce the plasma concentration of endoxifen which could lead to higher rates of BC recurrence. This resulted in an FDA black box warning discouraging concurrent prescriptions of tamoxifen and SSRIs, yet clinical data to support this warning is lacking. Our aim is to describe the practice patterns of concomitant use of tamoxifen and antidepressant medication at our institution. Methods: This is a single institution retrospective study that included adult women, ages 18-99, with stage I-IV BC, who received adjuvant tamoxifen and were taking an antidepressant medication between years 2016-2021. Patients were identified from a tumor registry database. Patient demographics and tumor characteristics were collected via electronic medical record. Results: A total of 419 patients met the inclusion criteria. At the start of tamoxifen therapy, 348 women were on at least one antidepressant, mostly for Major Depressive Disorder (86%). Of those women, 22% were prescribed a strong/moderately potent CYP inhibitor (paroxetine, fluoxetine, duloxetine, or bupropion) and 43% were prescribed weak or non-CYP inhibiting SSRIs (citalopram, escitalopram, fluvoxamine, and sertraline). The most commonly prescribed antidepressants at the start of tamoxifen, alone or in combination with a second antidepressant, were: venlafaxine (30%), escitalopram (17%), sertraline (13%), citalopram (12%) and duloxetine (10%). Main prescribers of antidepressants were primary care physicians (70%), psychiatrists (10%) followed by academic medical oncologists (7%) and regional medical oncologists (6%). Interestingly, the majority of women continued taking the same antidepressant after starting tamoxifen (76%) while, at least 10% of patients changed anti-depressant classes prior to starting tamoxifen, due to concern for drug-drug interaction. When a different class of antidepressant was chosen after starting tamoxifen (22%), serotonin and norepinephrine reuptake inhibitors (SNRIs) were the most frequent class (48%), followed by a different SSRI (42%). The time in which the antidepressant change occurred was variable, but most commonly prior to initiating tamoxifen. Conclusion: Concurrent use of tamoxifen and antidepressant medications is common. Theoretical risk of reduced efficacy of tamoxifen with inhibitors of CYP leads to medication changes for some but not all patients requiring tamoxifen and an antidepressant medication. This can have clinical implications as stability on a specific antidepressant is important for patients and adjustment may impact control of their mood disorder. In some cases, even if a drug-drug interaction was identified, some patients chose to continue their current antidepressant due to concerns of mood de-stabilization, and in other cases, aromatase inhibitors were started as an alternative. These findings highlight differences in practice patterns for which additional guidance may be helpful in bringing awareness and standardization to care. Citation Format: Mariah Ondeck, Bennett Osantowski, Nerea Lopetegui-Lia, Wei Wei, Alexandra Murray, Amanda Maggiotto, Halle Moore, Erin Roesch. Assessing practice patterns of antidepressant medication and tamoxifen use among patients with hormone receptor-positive breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-11-08.

356 The Effect of Regional Anesthesia on Breast Cancer Recurrence

OBJECTIVES/GOALS: To determine the impact of regional anesthesia (RA) on rates of breast cancer recurrence, breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use among patients who received regional anesthesia during primary breast cancer surgery. METHODS/STUDY POPULATION: Study population: Patients who underwent primary breast cancer surgery at Emory University and among a national patient cohort. Methods: This is a retrospective analysis of patients who underwent primary breast cancer surgery. Invasive breast cancer specific survival & breast cancer-specific survival will be estimated using Kaplan-Meier method and compared among patient groups. Cox proportional hazards will be utilized to estimate the unadjusted & adjusted risk of breast cancer recurrence and breast cancer-specific mortality between the two groups. RESULTS/ANTICIPATED RESULTS: We will present on our work comparing rates of breast cancer recurrence among patients who received regional anesthesia compared to patients who did not. DISCUSSION/SIGNIFICANCE: This study aims to establish the effect of regional anesthesia on breast cancer recurrence,breast cancer specific mortality, post mastectomy pain syndrome, and chronic opioid use following primary breast cancer surgery.

Abstract 3474: Racial disparities in receipt of surveillance mammography after breast cancer diagnosis

Abstract Background: The 5-year survival rate for breast cancer (BC) stands at an estimated 91%, with approximately 3.8 million BC survivors in the U.S. This large population of breast cancer survivors remains at risk of loco-regional recurrence, with variations noted across racial groups. White survivors face a locoregional breast cancer recurrence rate of 1.8%, whereas Black, Asian, and Hispanic survivors experience higher rates of 3.9%, 3.6%, and 3.1%, respectively. Notably, Black BC survivors with recurrent breast cancer exhibit a median survival time of 1.8 years compared with 3.6 years observed for White BC survivors. Current recommendations from the U.S. Preventative Services Task Force and the American College of Radiology advocate for surveillance through annual mammography and routine clinical visits following breast-conserving surgery and lumpectomies. However, there are gaps in the data available regarding disparities in the utilization of surveillance mammography by race/ethnicity. Thus, the goal of this study is to estimate race/ethnic disparities in surveillance mammography utilization and its impact on survival among breast cancer survivors at a large comprehensive cancer center. Methods: A retrospective cohort study of female breast cancer survivors ≥19 years diagnosed and/or treated at the Duke Cancer Institute (DCI) between 2014 and 2022 was conducted. Data was abstracted on patient socio-demographics, cancer type (invasive ductal and ductal in situ carcinomas) and utilization of surveillance mammography within 2-5 years post initial breast cancer diagnosis. Chi-squared testing will be used to analyze rates of mammography surveillance receipt among different races presenting with BC at DCI. Kaplan-Meier estimates will be used for analysis on survival. Results: A total of 10,904 women with a mean age of 43.7 years were included in the study. The study cohort is comprised of 69% non-Hispanic (NH) White, 24% NH Black, 2.2% Hispanic, 0.5% NH Native American, 1% NH other, and 3.2% NH Asian women. There were 1,791 cases of ductal in situ carcinomas and 9,113 invasive ductal carcinoma cases. NH Black women had the lowest 5-year relative survival rate (81.5%) of all represented racial groups: NH White 89.1%, Hispanic 95.3%, NH Native 87.8%, Asian 97.9%, and NH Other 88.0%. Ongoing analysis will be completed to estimate disparities in the use of post-treatment surveillance mammography amongst breast cancer survivors. Conclusions: This study will inform efforts to increase post-treatment surveillance and improve adherence to survivorship guidelines with the ultimate goal of reducing mortality disparities among breast cancer survivors. Citation Format: Jasmine G. Wilkerson, Frances Wang, Yadurshini Raveendran, Tomi Akinyemiju. Racial disparities in receipt of surveillance mammography after breast cancer diagnosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3474.

The association between complementary and alternative medicine use with breast cancer recurrence in Taif city, Saudi Arabia

Background: Breast cancer (BC) is the most common cancer among women worldwide. Among all types of cancer, 11.7% of cases diagnosed in 2020 were BC. Compare this to Saudi Arabia, where 28.8 out of every 100,000 women were diagnosed with BC. Furthermore, BC patients are more likely than other cancer survivors to use complementary and alternative medicine (CAM). Study aimed to investigate association between CAM use and BC recurrence rates in Saudi Arabia. Methods: A cross-sectional study was conducted on 106 participants recruited from breast surgery clinics. Targeted women were diagnosed with BC and treated at Al Hada armed forces hospital. The data were collected by interviewing the patients using a validated questionnaire. Results: The prevalence of CAM usage among BC patients was 35.8%. The recurrence rate of BC was 26.4%. CAM users accounted for 28.57% of the total, while non-CAM users comprised 71.43%. In addition, 50% of recurrences were distant metastases, and 50% occurred more than two years after diagnosis. Conclusions: In conclusion, more than one-third of BC patients in this region incorporate CAM into their treatment regimen. Our findings reveal a practical but not statistical significance of a lower recurrence rate of BC among CAM users compared to non-CAM. These results emphasize the importance of healthcare providers engaging in detailed discussions with BC patients regarding CAM usage in conjunction with planned medical and surgical therapies.

Increased risk of contralateral breast cancer for BRCA1/2 wild-type, high-risk Korean breast cancer patients: a retrospective cohort study

BackgroundThis study aimed to investigate the contralateral breast cancer (CBC) recurrence rate in Korean breast cancer patients according to their BRCA1/2 germline mutation status, focusing particularly on the CBC recurrence risk in BRCA1/2 negative (BRCAx) patients.MethodsWe conducted a retrospective study on 13,107 primary breast cancer patients. The patients were divided into high-risk and low-risk groups for hereditary breast cancer based on the Korean National Health Insurance Service’s eligibility criteria for BRCA1/2 germline mutation testing. The high-risk group was further categorized into the BRCAmutation group, the BRCAxgroup, and the not tested group. We evaluated the overall survival and cumulative risk of developing CBC in these patients.ResultsAmong 4494 high-risk patients, 973 (21.7%) underwent genetic testing for BRCA1/2 germline mutation, revealing mutations in 158 patients (16.2%). We observed significant overall survival differences across all four groups, with the high-risk, not-tested group demonstrating notably worse overall survival (p < 0.001). However, when adjusted for other prognostic factors, there was no significant differences in hazard ratio of death between the four groups. The cumulative risk of CBC also varied among the groups. Patients with BRCA1/2 mutations showed a 7.3-fold increased risk of CBC compared to the low-risk group (95% CI 4.11–13.0, p < 0.001). Interestingly, BRCAx patients also demonstrated a significantly higher risk of CBC (HR 2.77, 95% CI 1.76–4.35, p < 0.001). The prognostic importance of the BRCAx for CBC recurrence persisted after adjusting for the age and subtype, but became insignificant when the family history of breast cancer was adjusted.ConclusionBreast cancer patients who are at high risk of hereditary breast cancer but with wild-type BRCA 1/2 genes (BRCAx) have increased risk of developing contralateral breast cancer when compared to the low-risk patients. More careful surveillance and follow-up can be offered to these patients especially when they have family history of breast cancer.

Based on whole-exome sequencing to explore the rule of Herceptin and TKI resistance in breast cancer patients

BackgroundBreast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs).MethodsThere are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response.ResultsThe C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it.ConclusionsOur study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.

Nipple-sparing mastectomy in young versus elderly patients.

In this study, we compared indications and outcomes of 115 young (< 40 years) versus 40 elderly (> 60 years) patients undergoing nipple-sparing mastectomy (NSM) as risk-reducing surgery or for breast cancer (BC) treatment. Between January 2004 and December 2018, young and elderly patients undergoing NSM with complete data from at least 6 months of follow-up were included. BC treatment was the main indication for NSM, observed in 85(73.9%) young versus 33(82.5%) elderly patients, followed by risk-reducing surgery in 30(26.1%) young versus 7(17.5%) elderly patients. Complication rates did not differ between the age groups. At a median follow-up of 43 months, the overall recurrence rate was higher in the younger cohort (p = 0.04). However, when stratified into local, locoregional, contralateral, and distant metastasis, no statistical difference was observed. During the follow-up, only 2(1.7%) young patients died. Our findings elucidate a higher recurrence rate of breast cancer in younger patients undergoing NSM, which may correlate with the fact that age is an independent prognostic factor. High overall survival and low complication rates were evidenced in the two groups showing the safety of NSM for young and elderly patients.

Metal-Organic Framework-Based Nano-Activators Facilitating Microwave Combined Therapy via a Divide-and-Conquer Tactic for Triple-Negative Breast Cancer.

Aiming at the clinical problems of high recurrence and metastasis rate of triple-negative breast cancer, a divide-and-conquer tactic is developed. The designed nanoactivators enhance microwave thermo-dynamic-chemotherapy to efficiently kill primary tumors, simultaneously ameliorate the immunosuppressive microenvironment, activate the tumor infiltration of T lymphocytes, and enhance the accumulation and penetration of PD-1/PD-L1 immune agents, ultimately boosting the efficacy of immune checkpoint blocking therapy to achieve efficient inhibition of distal tumors and metastases. Metal-organic framework (MOF)-based MPPT nano-activator is synthesized by packaging chemotherapeutic drug Pyrotinib and immunosuppressant PD-1/PD-L1 inhibitor 2 into MnCa-MOF and then coupling target molecule triphenylphosphine, which significantly improved the accumulation and penetration of Pyrotinib and immunosuppressant in tumors. In addition to the combined treatment of microwave thermo-dynamic-chemotherapy under microwave irradiation, Mn2+ in the nano-activator comprehensively promotes the cGAS-STING pathway to activate innate immunity, microwave therapy, and hypoxia relief are combined to ameliorate the tumor immunosuppressive microenvironment. The released Pyrotinib down-regulates epidermal growth factor receptor and its downstream pathways PI3K/AKT/mTOR and MAPK/ERK signaling pathways to maximize the therapeutic effect of immune checkpoint blocking, which helps to enhance the antitumor efficacy and promote long-term memory immunity. This nano-activator offers a generally promising paradigm for existing clinical triple-negative breast cancer treatment through a divide-and-conquer strategy.

Assessing the impact of frequent mammography after breast cancer treatment from a single-institution retrospective analysis

Background Despite prior attempts to establish guidelines, many radiologists still recommend frequent (every six month) mammography after breast conserving surgery. Ideally this recommendation would be based on the incremental value (recurrences detected earlier) of non-annual screening, compared to the associated harm (from false positive results leading to patient distress, unnecessary biopsies/procedures and costs). The aim of this study was to analyze the outcomes of performing biannual mammograms at our institution in order to determine if this may provide any additional benefit to annual mammograms. Methods A retrospective analysis of 359 female patients with stage 0-III breast cancer who underwent breast-conservation surgery was performed. Data were obtained on breast cancer characteristics, imaging, pathology, and recurrence rates. Descriptive analyses were subsequently performed. Results A total of 569 6-month and 18-month mammograms were completed after breast-conservation therapy. This led to 22 biopsies, only one of which detected a recurrence (in a high-risk patient who was unable to complete recommended treatment). Conclusions The data suggest that annual surveillance mammography following breast conserving therapy (BCT) is likely sufficient for detection of recurrences, with increased screening leading to increased harm without benefit. More frequent screening should be limited to select high-risk patients.