Treatment Of Early Breast Cancer Research Articles

Abstract PO5-26-06: Understanding patient experiences to inform future studies to reduce treatment burden in breast cancer

Abstract Background Most patients with early breast cancer receive multimodality therapy, including surgery, chemotherapy, radiotherapy and endocrine therapy. Currently, not all patients benefit from the treatments they receive but many experience significant morbidities that substantially impact their quality of life. Personalised approaches to treatment offer the opportunity for patients to avoid treatments that do not offer oncological benefit without compromising breast cancer outcomes. Further studies are needed to evaluate these approaches; it is vital that future research is designed to optimise treatment benefit while remaining acceptable to patients. This survey aimed to understand experiences of patients who have received treatment for early breast cancer to inform future risk-adapted studies. Methods An online survey was co-developed with patient advocates to explore respondents’ experiences of treatments. Questions included simple demographics, treatments received and views about omitting therapies if it was safe to do so. Free-text boxes were provided for respondents to explain their decision. The survey was circulated via social media platforms from April-July 2023. Responses were summarised using simple descriptive statistics and free text was analysed thematically. Results 112 responses were received. Respondents were mostly aged 40-60 (n=88, 72.7%) and diagnosed with breast cancer between 1995 - 2023 (median 2017). Treatments received included surgery (n=107, 95.5%), radiotherapy (n=85, 75.9%), chemotherapy (n=69, 61.6%) and endocrine therapy (n=82, 73.2%). Of the 106 (94.6%) respondents who expressed a preference, 38 (35.8%) would omit chemotherapy; 34 (32.1%) would choose not to have endocrine therapy; 19 (17.9%) would prefer to avoid surgery and 11 (10.4%) would omit radiotherapy if safe to do so. Respondents opting to avoid chemotherapy highlighted the ‘brutal’ short-term side effects and their profound impact on their ability to continue with their daily lives. Hair loss was a common concern and chemotherapy was considered ‘very visible’, making them a ‘cancer patient’ in the eyes of others. Long-term effects of treatment such as peripheral neuropathy had lasting effects on respondents’ activities of daily living. Almost all respondents who would omit endocrine therapy cited the profound impact of side effects including joint/muscle pains, fatigue, hair loss, sleep disturbance and loss of libido on quality of life. Some respondents commented that the treatment itself was a daily reminder of their diagnosis. Surgery was identified as having long-term impacts on respondents’ physical and psychological well-being. Many expressed a desire to avoid ‘disfiguring’ procedures which had affected their relationships and quality of life. Respondents highlighted specific procedures they would choose to avoid including mastectomy due to the ‘trauma’ of losing a breast and axillary node clearance due to complications such as lymphoedema. Fewer women chose to avoid radiotherapy. Reasons to do so included both short and long-term side effects of treatment including chronic pain, difficulties travelling and attending for treatment over 5 weeks. Although there was generally a positive response to the concept of reducing unnecessary treatments, safety was a key concern. Several respondents commented that they would have any treatments considered necessary as survival was their ‘absolute priority’. Respondents felt that patients would need to be reassured that any reduction in treatment would not impact long-term outcomes. Conclusions This survey suggests patients would support studies aiming to reduce the burden of breast cancer treatment, and that different patients may wish to de-escalate different components of therapy. Studies developing an evidence base to allow treatment personalisation with a particular emphasis on reducing chemotherapy and endocrine therapy are research priorities. Citation Format: Shelley Potter, Mhairi MacTier, Katherine Fairhurst, Jacqui Gath, Hilary Stobart, Stuart McIntosh. Understanding patient experiences to inform future studies to reduce treatment burden in 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 PO5-26-06.

Abstract PO2-18-07: Ultrasound – guided Interstitial Laser therapy for Stage I Breast Cancer: a phase 2 trial

Abstract Background: Screening programs are changing the scope of breast cancer, with a growing number of patients diagnosed at a nearly stage. The current standard treatment (breast conservation and radiation therapy) offers an excellent prognosis for these patients. Besides tumor removal, other techniques can be used to destroy a mass in place. A range of minimally invasive techniques holds promise on local breast tumor ablation (i.e. thermotherapy, cryotherapy, and irreversible electroporation). Previous studies with Interstitial laser thermotherapy (ILT) for breast cancer report mean ablation rates between 33% to 87%. Most common cited causes for failure are equivocal tumor size estimation, inadequate technique and the learning curve. Objective: Improve the ILT technique and achieve better ablation rates through the evaluated procedure. Methods: A prospective study with 15 patients with Stage I invasive breast cancer, presented as a unique lesion as inclusion criteria was conducted. MRI and US were used to estimate the primary tumor volume and rule out multicentric/multifocal disease. ILT ablation was performed using an Echolaser unit (Elesta) through percutaneous laser optical fibers with a US-guided insertion in the lesion center. All procedures were performed under local anesthesia and sedation. The post procedure image reevaluation included an immediate US after the ablation and a new MRI about 3 hours after the procedure. The definitive proposed surgical treatment was carried out 8-13 days after the ILT ablation. Results: Eighteen patients were included in the study, of whom 14 (with 15 lesions) completed the protocol. The mean tumor size measured by MRI was 13.7 (4-20) mm. The mean treatment time was 10.1 minutes and all patients went home the same day, reporting only mild (78%) or moderate (22%) pain, controlled with analgesics. The mean ablation index, evaluated by H&E and CK8/18, was 61,5% (0 -93%) and when only tumors under 15 mm were considered the mean ablation index was 75% (30%-93%). The MRI performed after ablation procedure showed a large area of edema around the clip in all cases. The sensitivity and specificity to detect residual tumors were 1.0 and 0.84, respectively, when the residual tumors were larger than 15% of the original tumor size . Conclusions: These preliminary results suggest that laser therapy can eliminate viable neoplastic tissue in vivo. To achieve better results, standardization in patient selection, power and energy applied, should be considered. There are several advantages of ILT for breast cancer treatment, including preserving the structure and function of breast, no bleeding, no scaring and no radiation. More studies refining the technique should be conducted to allow the implementation of ILT as an alternative to surgical treatment in early breast cancer. Citation Format: Danielle Matsumoto, Silvio Bromberg, Marcus Corpa, Rodrigo Garcia, Guilherme Mariotti, Monica Rudner, Angela Waitzberg, Afonso Nazário, Gil Facina. Ultrasound – guided Interstitial Laser therapy for Stage I Breast Cancer: a phase 2 trial [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 PO2-18-07.

Abstract PO3-28-05: Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy

Abstract Relevance: Paclitaxel-associated peripheral polyneuropathy (PIPN) is one of the most common side effects that develop during treatment with drugs of the taxane group. In the treatment of early breast cancer with paclitaxel 80 mg/m2 weekly, 12 injections, PINP develops in 90% of patients of varying severity. The main symptoms are pain and numbness in the arms and legs, which is associated with the accumulation of paclitaxel in the ganglia of the spinal cord, as well as increased expression in the ganglia of the spinal cord of chemokines and cytokines, such as IL-1β, IL-8 and TNF-α, as well as CXCR4, RAGE, CXCL1, CXCL12, CX3CL1 and C3. We hypothesized that the severity of PIPN symptoms can be reduced by lowering the concentration of chemokines and cytokines in the blood by performing plasmapheresis sessions. Research methods: An open prospective study was carried out, the protocol of which was approved by the ethical committee. The study included 30 patients (100% women) aged 30 to 60 years (mean age 45 years) who developed PIPN during paclitaxel therapy 80 mg/m2, weekly, 12 injections. The severity of PIPN symptoms was assessed using a “visual analogue scale” (VAS). The results of the VAS evaluation varied from 6 to 8 points. Patients underwent 5 courses of membrane plasmapheresis with exfusion of 400-500 ml of plasma per session (20 ml per 1 kg of body weight), plasma loss was compensated with saline. Repeated procedures were performed once every two months for 6 months. Results: 30 patients underwent 15 procedures of therapeutic plasmapheresis within 6 months. In 21 patients (70%) there was a pronounced decrease in PIPN symptoms (VAS - 2-3 points), in 3 patients (10%) a moderate decrease in symptoms (VAS -5-6 points), in 6 (20%) no effect of plasmapheresis (VAS - 7-8 points). Approximately 15% of procedures were associated with adverse events, the most common of which were vasovagal reactions; 20% of patients had at least one adverse event. Conclusions: Given the subjective reduction in the severity of PIPN symptoms during courses of therapeutic plasmapheresis in more than 70% of cases, therapeutic plasmapheresis can be used as a symptomatic therapy for PIPN, however, taking into account the subjective assessment of the results by patients, there may be a risk of developing cognitive errors. Therefore, this method of therapy requires more thorough study. Citation Format: Sardor Abdugafforov, Vladimir Vorotnikov, Alexander Soynov, Tornike Mchedlidze, Igor Kopytich, Sofia Kim. Therapeutic Plasmapheresis as a Symptomatic Treatment for Paclitaxel-Associated Peripheral Polyneuropathy [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 PO3-28-05.

Abstract GS03-02: Mammographic surveillance in early breast cancer patients aged 50 years or over: results of the Mammo-50 non-inferiority trial of annual versus less frequent mammography

Abstract Introduction: Annual surveillance mammograms for an unspecified period, after treatment for early breast cancer, are widely practised in USA and Europe and represent a significant healthcare cost. Current UK guidelines recommend annual mammograms up to 5 years, then reverts to 3 year screening without specified risk stratification. Further evidence is needed to determine the optimum frequency and duration of mammographic surveillance. Methods: A multi-centre, randomised controlled, phase III trial of annual mammography versus 2-yearly for conservation surgery and 3-yearly mammograms for mastectomy patients up to 9 years. Women were eligible if aged 50 years or over at initial diagnosis of breast cancer (invasive or DCIS), and recurrence free 3 years post curative surgery. Primary outcome was breast cancer specific survival (BCSS). Secondary outcomes include recurrence free interval (RFI) and overall survival (OS). BCSS event was defined as deaths from breast cancer and RFI as any locoregional or distant invasive recurrence or new breast primary. 5000 women were needed to detect a 3% absolute non-inferiority (NI) margin for BCSS with 2.5% one-sided alpha and at least 85% power. Analyses were carried out on intention-to-treat basis. Results: 5235 women were randomised between April 2014 and September 2018. 4347 (83%) women were aged 55-75 years, 4203 (80%) had undergone conservation surgery, 4564 (87%) had invasive disease, 1162 (22%) had node positive disease, 4330 (83%) had ER positive tumours and 3812 (73%) were taking hormone therapy at the time of randomisation. Patient characteristics were balanced across arms. With a median of 5.4 years follow-up (interquartile range 4.6-5.9), 319 women have died; 104 of breast cancer (53 on annual arm; 51 on less frequent arm). BCSS at 5 years was 98.2% (95% CI 97.5-98.6%) on annual arm and 98.3% (95% CI 97.7-98.8%) on less frequent arm. Hazard ratio (HR) was 1.04 (95% CI 0.71 -1.54), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p< 0.0001; critical value 2.71) and the 1% margin (NI p=0.02; critical value 1.56). 320 (6%) women had a new invasive breast cancer event (55 loco-regional recurrences, 85 new breast primaries, 139 distant recurrences and 41 with multiple invasive events); 164 on the annual arm compared to 156 on the less frequent arm. Five-year RFI was 94.2% (95% CI 93.2-95.1%) for the annual arm and 94.4% (95% CI 93.4-95.3%) for the less frequent arm; HR= 1.03; (95% CI 0.83-1.28) demonstrating non-inferiority at a 2% margin (NI p=0.006; critical value 1.36). OS at 5 years was 94.9% (95% CI 93.9-95.7%) on the annual arm and 94.3% (95% CI 93.3-95.2%) on the less frequent arm. Hazard ratio (HR) was 1.18 (95% CI 0.94 -1.47), demonstrating non-inferiority of less frequent mammograms at the 3% margin (NI p=0.003; critical value 1.61) and the 2.5% margin (NI p=0.02; critical value 1.51). A total of 14987 mammograms have been performed on the annual arm and 8047 on the less frequent arm. 1967 (75%) of 2618 women on the annual arm complied with their allocated schedule compared to 1775 (68%) of 2617 women on the less frequent arm. COVID-19 pandemic affected compliance; it is estimated that 345 (7%) women missed mammograms during the pandemic. A sensitivity analysis was performed on the 72% of women who fully complied with their scheduled mammograms as per protocol, and again NI was demonstrated for BCSS, RFI and OS. Conclusions: For patients aged 50 or older and 3 years post diagnosis, Mammo-50 demonstrated that less frequent mammograms were no worse than annual mammograms. These results provide evidence for less frequent mammographic surveillance for this patient population. Citation Format: Janet Dunn, Peter Donnelly, Nada Elbeltagi, Andrea Marshall, Alastair Thompson, Riccardo Audisio, Sarah Pinder, David Cameron, Amy Campbell, Sue Hartup, Lesley Turner, Annie Young, Helen Higgins, Eila Watson, Sophie Gasson, Peter Barrett-Lee, Claire Hulme, Bethany Shinkins, Peter Hall, Andy Evans. Mammographic surveillance in early breast cancer patients aged 50 years or over: results of the Mammo-50 non-inferiority trial of annual versus less frequent mammography [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 GS03-02.

Abstract PO2-09-12: The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort

Abstract Objective Previous studies showed that various outcomes in patients with early breast cancer (EBC), from incidence to survival, were influenced by social factors. However, there is limited research on the socioeconomic inequalities in quality of life (QoL) after treatment for EBC, and the magnitude and changes over time of these inequalities have not been quantified. This study examines the socioeconomic inequalities in QoL and their time trends among a large cohort of patients with EBC. Methods We conducted a comprehensive longitudinal analysis using data from the prospective multicentric CANTO study (CANcer TOxicity, NCT01993498), which included participants with EBC enrolled between 2012 and 2018. QoL was assessed using the summary score of the EORTC QLQ-C30 questionnaire at the time of diagnosis and 1 and 2 years post-diagnosis. We included patients with complete QoL data at diagnosis and 2 years post-diagnosis. Analyses were conducted for three indicators of socioeconomic status separately: self-reported financial difficulties, household income and educational level. We first analyzed trajectories of QoL by socioeconomic status from diagnosis to Year 1 and Year 2. Then, social inequalities in QoL were estimated using the regression-based slope indexes of inequality (SII) and compared across the follow-up periods. The SII represents the absolute change in the QLQ-C30 summary score along the two extremes of the socioeconomic gradient, taking into account the intermediate groups and their relative sizes. The analyses were adjusted for age at diagnosis, Charlson comorbidity index, disease stage, use and type of endocrine therapy, use and type of chemotherapy, breast surgery, radiotherapy use, and lymph node management. Results In the 5915 analyzed patients, compared to those with higher socioeconomic status, those reporting a high level of financial difficulty, lower income, or lower education were younger, most often premenopausal, with comorbidities, diagnosed with stage III BC, and treated with mastectomy and axillary lymph node dissection. There were no differences between socioeconomically-defined groups concerning BC histology, grade and IHC-defined subtype. Social inequalities in QoL at baseline were statistically significant for all socioeconomic status indicators (SIIfinancial difficulties = -7.6 [-8.9;-6.2], SIIincome= -4.0 [-5.2;-2.8]) and SIIeducation= -1.9 [-3.1;-0.7]). In multivariable analyses, social inequalities significantly increased (interaction p< 0.05) in Year 1 (SIIfinancial difficulties = -11.1 [-12.8;-9.4], SIIincome= -6.5 [-8.0;-5.0] and SIIeducation= -5.0 [-6.6;-3.5]) and Year 2 (SIIfinancial difficulties = -10.7 [-12.2;-9.1], SIIincome= -6.7 [-8.0;-5.3] and SIIeducation= -4.7 [-6.1;-3.3]) suggesting a widening socioeconomic gap in QoL outcomes irrespective of pre-diagnosis health, tumor characteristics and treatment. Similar results were observed in subgroups defined by menopausal status (pre/postmenopausal) and type of systemic treatment (chemotherapy, endocrine therapy). Conclusion Our study highlights and quantifies the association of several individual socioeconomic indicators with the QoL of patients with EBC in France. The magnitude of socioeconomic inequalities in QoL increased over time after EBC diagnosis in a country with a strong welfare system and universal healthcare coverage. In the era of precision medicine, these results underscore the importance of developing interventions to improve precision care, considering the conditions in which people are born, grow, work, live and age and the wider set of forces and systems shaping the conditions of daily life. Citation Format: José Luis Sandoval, Antonio Di Meglio, Arlindo Ferreira, Maria Alice Franzoi, Fabrice André, Barbara Pistilli, Christelle Jouannaud, Marion Fournier, Philippe Rouanet, Asma Dhaini Mermeche, Paul Cottu, Sibille Everhard, Anne-Laure Martin, Silvia Stringhini, Idris Guessous, Ines Vaz Luis, Gwenn Menvielle. The magnitude and temporal variations of socioeconomic inequalities in quality of life after early breast cancer: results from the multicentric French CANTO cohort [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 PO2-09-12.

Abstract PO5-19-01: The HER2-RADiCAL study (Response ADaptive CAre pLan) – Tailoring treatment for HER2 positive early breast cancer

Abstract Background The presence or absence of residual disease following neoadjuvant systemic anti-cancer therapy (neoSACT) for HER2-positive early breast cancer (HER2+ EBC) provides powerful prognostic information. Pathological complete response (pCR) following neoSACT, particularly in patients with earlier clinical TNM stage at diagnosis, identifies a population with excellent survival outcomes in whom the balance of toxicity associated with the current treatment pathway may be disproportionate to absolute clinical benefit. Aims >HER2-RADiCAL seeks to reduce the treatment burden and healthcare costs of treating HER2+ EBC by testing the hypothesis that pCR can be used as a functional response biomarker to select patients who can safely receive less systemic therapy with minimal/no loss of efficacy. Trial design and eligibility criteria HER2-RADiCAL is a response-directed interventional cohort/threshold-crossing design study embedded within a real-world data-driven clinical pathway model. Patients with ER-positive or negative HER2+ EBC with cT1N1 or cT2N0-1 stage at diagnosis are eligible after completion of standard of care neoSACT and locally determined pCR (ypT0/Tis ypN0). Patients with pathological features consistent with previous malignant involvement in >4 nodes are not eligible. Adjuvant trastuzumab +/- pertuzumab may have continued prior to study entry provided no more than 9 cycles of trastuzumab are received. After registration all participants receive a total of 9 cycles of trastuzumab including those administered prior to study entry. Participants receive no further pertuzumab and no adjuvant chemotherapy. Adjuvant endocrine therapy and radiotherapy are given as per standard of care. Central pathology review of pCR status will be conducted in a subset of cases. A Study Within a Trial (SWAT) will explore identification of factors influencing patient decision-making for participation in studies of response-adapted treatment. Statistical methods The primary endpoint is relapse-free interval. Recruitment of 720 participants over 3.5 years will provide 90% power to exclude an event rate >6.5% at 3 years (expected event rate ≤4%). Secondary endpoints include relapse-free survival, invasive breast cancer-free survival, invasive disease-free survival, distant recurrence-free interval, breast cancer-free interval, overall survival, treatment pathway adherence and cost-effectiveness. An interventional cohort is preferred to a randomised non-inferiority trial based on the known event rate in this population which is sufficiently low such that any deviation from this expected event rate would indicate failure of the reduced therapy strategy. Real-world data driven clinical pathway model Health economic modelling will compare the protocol-driven study cohort with two comparator pathways: a non-response adapted maximum therapy pathway (the standard clinical pathway prior to the study) and a real-world representative pathway derived from anonymised data for all patients treated for HER2+ EBC within the UK NHS. Patient and public involvement Our PPI partners continue to shape this research, holding key roles as trial management group members, overseeing progress of the study, contributing to protocol amendment development, and design and implementation of the SWAT. Current status The first patient was enrolled in December 2021. At 10th July 2023, 25 research sites have opened with 39 participants recruited. Site opening continues with a minimum target of 40. Responding to continued use of anthracycline-based regimens in UK practice, eligibility criteria have recently been extended to permit entry of patients who have received anthracycline-containing neoSACT. For further information contact her2radical-icrctsu@icr.ac.uk. Citation Format: Iain Macpherson, Stuart McIntosh, Lucy Kilburn, Holly Tovey, Laura Moretti, Katie Goddard, Indrani Bhattacharya, Clinton Boyd, Cliona Kirwan, Ciara O'Brien, Duncan Wheatley, Jennifer Glendenning, Mairead MacKenzie, Hilary Stobart, Claire Snowdon, Andrew Wardley, Abeer Shaaban, Peter Hall, David Cameron, Judith Bliss. The HER2-RADiCAL study (Response ADaptive CAre pLan) – Tailoring treatment for HER2 positive early 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 PO5-19-01.

Abstract PO2-03-12: Dose-Dense Doxorubicin plus Cyclophosphamide (ddAC) and Impact of Chemotherapy Sequence in a Modified KEYNOTE-522 Regimen for Neoadjuvant Treatment of Triple Negative Breast Cancer: Real World Experience

Abstract Background: Standard of care systemic treatment for early stage triple negative breast cancer (TNBC) consists of neoadjuvant chemoimmunotherapy based upon the results of KEYNOTE 522 (KN-522). The KN522 regimen utilized q3week dosing for doxorubicin plus cyclophosphamide (AC); however, dose-dense AC (ddAC) has shown superior OS compared to q3week AC in anthracycline and taxane-based regimens (per CALGB 9741 and EBCTCG analyses). We now present a retrospective study of patients treated with ddAC in a modified KN-522 regimen and report real world feasibility, safety, and efficacy endpoints, including exploration of whether sequencing ddAC before or after carboplatin/paclitaxel (CbT) plus pembrolizumab impacts outcome. Methods: Patients with TNBC treated at MSK from August 2021 to September 2022 with a preoperative KN-522 regimen were eligible for inclusion. Clinicopathological and demographic data were obtained from chart review. The primary goal of this study was to describe pathologic complete response (PCR) rate, incidence of treatment-related toxicities resulting in treatment delays, and type of toxicity. Treatment delays for toxicity were defined as a >1 week delay in treatment or discontinuation of a treatment regimen component due to a medical reason. Exploratory analysis was conducted to assess efficacy and toxicity of ddAC before or after CbT as well as rate of GCSF usage with CbT. Baseline characteristics, incidence and type of delays, and treatment outcomes were compared between ddAC first and CbT first using two sample non-parametric tests. Results: 129 TNBC patients met eligibility as defined above. Median age of diagnosis was 50. Clinical stage at diagnosis: Stage I 6%, Stage II 83%, and Stage III 11%. 128 patients received ddAC and 1 patient received AC q3week. Of the 128 patients, 54% received ddAC first while 46% received CbT first. Overall PCR rate of 56%. Treatment-related toxicity leading to chemotherapy delays was 61% and immunotherapy delays was 30%. Most chemotherapy delays were due to cytopenias (79%), with neutropenia (66%) most common. Adrenal insufficiency (4%) and hepatitis (5%) were the most common immune-related toxicities leading to delays. Overall, PCR rate was not affected by chemotherapy delays (No Delay 50% vs. Delay 60%, RR 0.83, 95%CI 0.60-1.15, p=0.25) or immunotherapy delays (No Delay 56% vs. Delay 58%, RR 0.96, 95%CI 0.69-1.33, p=0.81). Exploratory analysis comparing sequencing of ddAC vs CbT first showed incidence of CbT delays was 58% in patients treated with ddAC first and 27% in CbT first. Incidence of ddAC delays was 3% in patients treated with ddAC first and 7% in CbT first. Incidence of delays in both ddAC and CbT was 9% in ddAC first and 10% in CbT first. There was no difference in PCR rate (ddAC 55% vs. CbT 58%, RR 0.96, 95%CI 0.70-1.30, p=0.77) or rate of immunotherapy delays (ddAC 32% vs. CbT 34%, RR 0.93, 95%CI 0.55-1.57, p=0.79) based on sequence of chemotherapy. However, ddAC first compared to CbT first correlated with a significant increase in the incidence of overall treatment delays (ddAC 70% vs. CbT 51%, RR 1.37, 95%CI 1.02-1.84, p=0.03), use of GCSF during CbT (ddAC 55% vs. CbT 34%, RR 1.60, 95%CI 1.06-2.45, p=0.02), and treatment-limiting cytopenias at any time point before surgery (ddAC 59% vs. CbT 31%, RR 1.95, 95%CI 1.26-3.00, p=0.001). Conclusions: These real world data support the feasibility and tolerability of ddAC in a modified KN522 regimen. Exploratory analysis on sequencing of ddAC vs. CbT first in this regimen suggests that efficacy is comparable, yet ddAC first is significantly associated with higher rates of treatment delays and cytopenias. Overall, our experience suggests ddAC is a safe and viable modification to KN-522, and sequencing ddAC after CbT may reduce the risk of treatment induced cytopenias. Citation Format: Nicholas Mai, Sara Myers, Sherry Shen, Stephanie Downs-Canner, Yuan Chen, Tiffany Traina, Nour Abuhadra. Dose-Dense Doxorubicin plus Cyclophosphamide (ddAC) and Impact of Chemotherapy Sequence in a Modified KEYNOTE-522 Regimen for Neoadjuvant Treatment of Triple Negative Breast Cancer: Real World Experience [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 PO2-03-12.

Abstract PO4-03-12: De-escalating treatment with neoadjuvant chemotherapy in early triple-negative breast cancer

Abstract Neoadjuvant chemotherapy (NAT) is a standard treatment in early triple-negative breast cancer, but the regimen and duration of this treatment are controversial. We analyze a cohort of early triple negative breast cancer treated with NAT with different schemas to determine its efficacy. 272 patients treated with NAT since 2001 to 2020 were selected. The median age of the group was 57 years (27-85), initial size 30 mm (9-122) and Ki67 expression was 60 (7-100). 107 patients (39.3%) had histologically confirmed initial axillary involvement and the regimens of chemotherapy used were carboplatin AUC 5 + weekly paclitaxel (80 mg/m2) x 4 cycles in 56 cases (21%) (SCHEME A), same scheme followed by 4 cycles of adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 in 85 cases (31%) (SCHEME B), Adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 × 4 cicles in 44 (16%) (SCHEME C) and Adriamycin 50 mg/m2 + cyclophosphamide 500 mg/m2 × 4 cicles followed by docetaxel 100 mg/m2 × 4 cicles in 87 (32%) (SCHEME D). We achieved a 51% of pathologic complete response (pCR),and a total of 24% of recurrences. The proportion of PCR and recurrence according to the different schemes is represented in the following table. The clinical factors associated with recurrence were the initial size (OR 8.6), the initial axillary involvement (OR 4.21) and the absence of pCR (OR 8.14), and for patients with pCR it was only the initial axillary involvement (OR 3.4). Patients that received schema A in NAT only presented a total of 5% of recurrence (3/56), only in patients with initial axillary involvement. The NAT schema with carboplatin AUC 5 + weekly paclitaxel (80 mg/m2) x 4 cycles is safe in patients without initial nodal involvement with high pathologic complete response (62%) and lower recurrence rate (9% in nonPCR and 3% in pCR). Therefore, it could be considered as a standard scheme of neoadjuvant chemotherapy for patients without axillary involvement. Table. SCHEMA A (20%) B (31%) C (16%) D (32%) Pcr 62% 63% 41% 37% Recurrence in pCR 3% 7% 16% 9% Recurrence in nonpCR 9% 16% 50% 63% Citation Format: Serafin Morales Murillo, Ariadna Gasol Cudós, Noemí Tuset Der-Abrain. De-escalating treatment with neoadjuvant chemotherapy in early triple-negative 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 PO4-03-12.

Abstract PO5-12-07: Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation

Abstract Understanding the early breast cancer (eBC) patient experience of disease and treatment is critical to addressing unmet patient needs, improving outcomes, and informing the next wave of drug development. Traditional approaches, such as interviews or focus group studies, are resource intensive and have limitations in reflecting the diverse experiences of patients with different disease characteristics, treatments, and sociodemographic backgrounds, and in detecting rare severe events that could potentially lead to therapy discontinuation. To overcome these limitations, we have developed a semi-automated approach utilizing Natural Language Processing (NLP) and Machine Learning (ML) methods in application to public patient forums to extract patient insights. Specifically, we analyzed 500,000 anonymized posts from the BreastCancer.org forum, utilizing Transformer-based methods to identify posts related to eBC patient experiences treated with standard hormonal therapies (HT). First, a novel ML-based model identified posts related to eBC adjuvant HT. For those, patient demographics, symptoms and their severity, and symptom management strategies such as exercise and yoga were subject to further analysis. Out of 362,074 relevant eBC posts, 32 symptoms and 9 impacts were significantly associated with at least one of the six hormonal therapies we considered. Hot flushes (relative risk [RR]: 6.70; 95% CI: 3.36–13.36), arthralgia (RR: 6.67; 95% CI: 3.53–12.59), weight increase (RR: 4.83; 95% CI: 3.20–7.28), mood swings (RR: 7.36; 95% CI: 5.75–9.42), insomnia (RR: 4.76; 95% CI: 3.14–7.22), and depression (RR: 3.05; 95% CI: 1.71–5.44) demonstrated the strongest associations. Severe headache, dizziness, back pain, and muscle spasms showed significant associations with ≥1 HT despite their low overall prevalence in eBC posts. Notably, posts contained a wide range of symptoms severity, including rarely seen symptoms in smaller patient pools, such as severe night hot flashes leading to treatment discontinuation. Symptoms/impacts mentioned in association with exercise and yoga as a way for symptom mitigation included hot flashes, arthralgia, fatigue, anxiety, depression, and pain. Of those posts, 53.3% to 82.5% reported positive or neutral sentiments for exercise, and 22.2% to 100.0% for yoga. For posts specifically mentioning the management of side effects of HT, between 50.0% and 63.5% had a positive sentiment associated with exercise concerning each of the symptoms/impacts with a lower positive impact related to yoga (between 11.1% and 43.0% of posts). Posts discussing pain management and exercise included a higher proportion of negative feedback, versus positive sentiment for depression. Posts related to yoga as an HT symptom mitigation strategy had a higher prevalence of negative sentiments for anxiety and depression. Our proposed ML/NLP-based approach to collecting patient feedback from publicly available forums complements standard qualitative methods by enabling the scalable extraction of insights from hundreds of thousands of online conversations that could span a broad diversity of symptoms and well-being reflections. Furthermore, our findings suggest the potential value of informing clinical outcome assessment (COA) measurement for clinical trials, alone and in combination with standard qualitative research approaches to guide the next clinical development. Overall, our study highlights the significant potential of NLP and ML to address the critical need to better understand the eBC patient experience of disease and treatment to improve outcomes for patients. Citation Format: Sameet Sreenivasan, Chao Fang, Emuella Flood, Natasha Markuzon, Jasmine Sze. Analyzing Patient Experiences with Adjuvant Hormone Therapy for Early Breast Cancer Treatment via NLP/ML on Social Media: Symptoms and Their Mitigation [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 PO5-12-07.

Abstract Db1-01: Anthracyclines …to give or not to give? “For” argument

Abstract Anthracyclines have been one of the mainstays of early breast cancer treatment for decades. In a recent patient-level meta-analysis including data from over 18,000 patients, anthracycline-containing regimens were associated with improvements in disease-free survival and overall survival, regardless of estrogen receptor or nodal status. Importantly, trials specifically designed and powered to assess the safety of anthracyclines omission failed to demonstrate the non-inferiority of taxane-based anthracycline-free regimens and confirmed the benefit of these agents, particularly in patients with node-positive and hormone receptor-negative breast cancer. Several therapies incorporated into the management of early breast cancer were studied in populations largely treated with anthracycline-based chemotherapy backbones in both HER2-negative (i.e., perioperative pembrolizumab, post neoadjuvant olaparib and capecitabine) and HER2-positive disease (i.e., dual HER2 blockade, adjuvant T-DM1). It is uncertain whether the benefits demonstrated by these strategies would be maintained if anthracyclines were omitted. While anthracyclines are associated with some long-term toxicities, particularly with an increased risk of lymphoproliferative malignancies and dose-dependent cardiotoxicity, these adverse events are not associated with an increased risk of death (including deaths from cardiovascular causes) when compared to anthracycline-free regimens. The identification of risk factors for cardiotoxicity, combined with improvements in monitoring strategies, allows improvements in patient selection, early detection of myocardial damage and, possibly, implementation of cardioprotective interventions, leading to improved cardiovascular outcomes. Until high-quality evidence demonstrates the safety of omitting anthracyclines in high-risk populations, these agents should continue to be used in carefully selected patients after individual risk versus benefit assessment to be shared with the patient. Citation Format: Martine Piccart, Guilherme Nader-Marta. Anthracyclines …to give or not to give? “For” argument [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 Db1-01.

Impact of neoadjuvant pembrolizumab adherence on pathologic complete response in triple-negative breast cancer: a real-world analysis.

The addition of pembrolizumab (pembro) to neoadjuvant chemotherapy (NAC) is standard of care for the treatment of early triple-negative breast cancer (TNBC) after KEYNOTE-522 trial demonstrated improved pathologic complete response (pCR) rates with the combination. However, the optimal treatment strategy for TNBC remains uncertain as questions persist about which patients benefit from pembro and the best treatment schedule and regimen. We identified real-world clinical characteristics and treatment variables associated with response to NAC plus pembro. Patients with early TNBC treated with NAC plus pembro between February 2020 and September 2023 were identified. Univariate and multivariate analysis was performed using logistic regression to identify factors associated with pCR. Cox proportional hazard prediction models were used to identify predictors of invasive disease-free survival and overall survivalin this cohort. A pCR was achieved in 75 (63.6%) of 118 patients. Age at diagnosis (P = .04), Ki-67 (P = .004), duration from start of pembro to surgery (P = .006) and NAC to surgery (P = .01), number of cycles of pembro (P = .04) and NAC (P = .02), and completion of at least 8 cycles of pembro (P = .015) and NAC (P = .015) were each significantly associated with pCR in univariate analysis. In multivariate analysis, patients younger than 55 years at time of diagnosis (vs age > 55 years) and those completing at least 8 cycles of pembro remained predictive of pCR (OR's 2.50, 2.49, P = .035 and .037, respectively). In this real-world analysis of patients with TNBC treated with NAC plus pembro, younger age and the completion of at least 8 cycles of pembrolizumab were associated with pCR.

Protocol for the development of a core outcome set and reporting guidelines for locoregional treatment in neoadjuvant systemic breast cancer treatment trials: the PRECEDENT project

IntroductionNeoadjuvant systemic anticancer therapy (neoSACT) is increasingly used in the treatment of early breast cancer. Response to therapy is prognostic and allows locoregional and adjuvant systemic treatments to be tailored...

Treatment patterns, healthcare resource utilization and outcomes for early stage triple-negative breast cancer in Japan.

Aim: There is limited information regarding the treatment and outcomes of early stage triple-negative breast cancer (esTNBC) in real-world settings in Japan. Materials & methods: Retrospective analyses of the Medical Data Vision database assessed treatment patterns, healthcare resource utilization (HCRU), patient characteristics, outcomes and prognostic factors among four groups (neoadjuvant therapy+surgery+adjuvant therapy; neoadjuvant therapy+surgery; surgery+adjuvant therapy; surgery only) of esTNBC patients. Results: Treatment patterns, HCRU and demographics varied among the four groups. HCRU was greater and prognosis tended to be worse in the neoadjuvant+surgery+adjuvant therapy group. Conclusion: Our results provide insights into the treatment practices, HCRU and prognosis of esTNBC in Japan. The treatment practices were heterogeneous, reflecting the decision-making process in Japan during the study period.

A Scoping Review of the Knowledge and Practice of Breast Self-Examination among Women in Nigeria

Over 19 million cases of breast cancer were reported among women in 2020, surpassing lung cancer to become the leading cause of cancer worldwide. Women in developing countries have higher mortality rates than women in developed countries. Breast self-examination (BSE) is a simple procedure carried out by women themselves to determine any changes in their breasts and if needed seek further medical attention. This scoping review aimed to assess the available evidence on the knowledge and practice of BSE among women in Nigeria. This scoping review was conducted by searching African Journals On-Line (AJOL), ProQuest, PubMed and Science Direct databases for eligible studies. The relevant data was then extracted and a summary of the findings reported. 36 eligible articles were identified, 15 studies met the inclusion criteria and were considered for data extraction. All the studies included were cross-sectional descriptive surveys. The average reported knowledge of BSE is 67%, with 40% of study respondents practicing BSE, but only 26% of study respondents practiced BSE monthly. There’s low practice of BSE among women in Nigeria. Further research and appropriate interventions are needed to improve early detection and treatment of breast cancer.

Comparison of the effectiveness of intraoperative radiotherapy with external beam radiotherapy in patients with early breast cancer

Background. Breast cancer is the most common cancer in women. The main treatment for breast cancer includes surgery, chemotherapy, radiation therapy, and hormone therapy. The role of radiation therapy in the management of breast cancer continues to evolve. Radiation therapy is currently being de-escalated to include the use of intraoperative radiotherapy (IORT) and adjuvant endocrine therapy. Purpose of the study: to compare the efficacy of IORT with that of external beam radiotherapy (EBRT) in the treatment of early breast cancer. Material and Methods. A retrospective study of 559 patients with early breast cancer was conducted in Clinical Oncology Center of Saint Petersburg. The main treatment group included 273 patients who underwent breast-conserving surgery with IORT and sentinel lymph node biopsy. The control group included 286 patients who underwent breast-conserving surgery with sentinel lymph node biopsy and EBRT. Results. For all patients, the median follow-up time was 59.1 months (interquartile range: 43.7 to 80.7), the minimum follow-up period was 0.6 months, and the maximum follow-up period was 110.4 months. Recurrence occurred in 18 (6.6 %) patients of the main group and in 8 (2.8 %) patients of the control group. A statistically significant association of biological subtype with survival outcomes was found (p=0.02). The hazard ratio for Luminal B of 1.88 (95 % CI 1.02, 3.46) corresponded to a 65 % chance of an earlier onset of a negative outcome. The hazard ratio for triple-negative breast cancer of 3.01 (95 % CI 1.53, 5.95) corresponded to a 75 % chance of an earlier negative outcome. In the main treatment group, 11 (4 %) patients developed disease progression, and 2 of them died of multiple organ failure. In the control group, disease progression was observed in 18 (6.3 %) patients, 6 of whom died. However, the analysis of overall survival using the Kaplan–Meier curve showed a statistically non-significant log-rank p-value (0.73). The 3-year survival rates were 100 % (100 – 100) in the treatment group and 98.2 % (96.7 – 99.8) in the control group. The 5-yaer survival rates were 99.3 % (97.9 – 100) in the treatment group and 97.8 % (96.2 – 99.6) in the control group. These results showed advantage of IORT over EBRT. Conclusions. Intraoperative radiotherapy is a safe and effective alternative to external beam radiotherapy for early breast cancer.

Feasibility of targeted therapies in the adjuvant setting of early breast cancer in men: real-world data from a population-based registry

BackgroundFollowing the positive iDFS and OS results of the phase III clinical trials monarchE, NATALEE and OlympiA, new oral anticancer agents (the CDK4/6 inhibitors abemaciclib, ribociclib as well as the PARP inhibitor olaparib) have recently been introduced into the treatment of high-risk early breast cancer (eBC). However, only few male patients were included in these trials (0.4%, 0.6% and 0.3%, respectively). The objective of this real-world analysis was to determine the proportion of male patients with eBC fulfilling the clinical high-risk criteria of above-mentioned trials.Patients and methodsWe conducted a data inquiry and analysis with the Cancer Registry of Baden-Württemberg of men with breast cancer diagnosed between January 1, 2015 and December 31, 2021. Men with eBC were identified and the number of patients at clinical high-risk according to the inclusion criteria of monarchE, NATALEE and OlympiA was assessed.ResultsOf 397 men with eBC, 354 (89.1%) had a HR + /Her2− and 4 (1.0%) a triple-negative subtype. 84 patients (21.2%) met the clinical high-risk criteria according to the monarchE, 189 (47.6%) those according to the NATALEE and 50 (12.6%) those according to the OlympiA trial.ConclusionIn a large real-world sample, more men with eBC are at clinical high risk according to the inclusion criteria of monarchE, NATALEE and OlympiA than would be expected in women. This is most likely due to more advanced stages at initial diagnosis in men. To evaluate whether CDK4/6 and PARP inhibitors improve prognosis also in men should be the topic of future real- world analyses.

Study on breast cancer image detection and classification based on residual connected convolutional neural network (CNN)

This paper presents a method for breast cancer image detection and classification based on convolutional neural networks. While traditional breast cancer detection methods carry the risk of subjectivity and misclassification, machine learning can improve the accuracy and efficiency of detection by training algorithms to automatically identify breast cancer lesions in patients. The dataset of this paper includes 7909 microscopic images of breast tumor tissues with different magnifications collected from 82 patients, which are divided into two categories: benign and malignant tumors. In this paper, residual connection is designed for convolutional neural networks, which is a cross-layer connection method that can effectively solve the gradient vanishing and gradient explosion problems in deep neural networks, and at the same time, improve the generalization ability and training speed of the model. In this paper, the dataset is divided into training set, validation set and test set according to the ratio of 6:2:2. Through training and validation, the prediction accuracy of the obtained model on the test set reaches 85.5%, which achieves good prediction results in breast cancer image detection and classification. Eventually, the model's loss converged at 0.53 and the AUC was 0.832. The research results in this paper are of great significance for the early diagnosis and treatment of breast cancer. Automatic identification and classification of breast cancer images by machine learning algorithms can reduce the subjective judgment of doctors, improve the accuracy and efficiency of detection, and provide important support for the early diagnosis and treatment of breast cancer. Meanwhile, the research method and results of this paper also provide reference and reference for image detection and classification of other malignant tumors.

DNA Methylation-Based Diagnosis and Treatment of Breast Cancer.

DNA methylation is a key epigenetic modifier involved in tumor formation, invasion, and metastasis. The development of breast cancer is a complex process, and many studies have now confirmed the involvement of DNA methylation in breast cancer. Moreover, the number of genes identified as aberrantly methylated in breast cancer is rapidly increasing, and the accumulation of epigenetic alterations becomes a chronic factor in the development of breast cancer. The combined effects of external environmental factors and the internal tumor microenvironment promote epigenetic alterations that drive tumorigenesis. This article focuses on the relevance of DNA methylation to breast cancer, describing the role of detecting DNA methylation in the early diagnosis, prediction, progression, metastasis, treatment, and prognosis of breast cancer, as well as recent advances. The reversibility of DNA methylation is utilized to target specific methylation aberrant promoters as well as related enzymes, from early prevention to late targeted therapy, to understand the journey of DNA methylation in breast cancer with a more comprehensive perspective. Meanwhile, methylation inhibitors in combination with other therapies have a wide range of prospects, providing hope to drug-resistant breast cancer patients.

123 (PB-123) Poster - A Multicountry Discrete Choice Experiment (DCE) to Understand Patients’ Preferences for HR+/HER2− Early Breast Cancer (EBC) Treatments

123 (PB-123) Poster - A Multicountry Discrete Choice Experiment (DCE) to Understand Patients’ Preferences for HR+/HER2− Early Breast Cancer (EBC) Treatments

2023 Year in review: Early breast cancer

The results of several studies aiming to tailor early breast cancer treatment to individual risk were released in 2023. Axillary lymph node dissections and radiotherapy may be safely omitted in carefully selected patients. Sustained benefit from adjuvant CDK4/6 inhibitors was observed in high-risk hormone receptor-positive disease and the addition of immunotherapy to neoadjuvant chemotherapy improved pathological response. Continued benefit from perioperative pembrolizumab was reported in patients with triple negative breast cancer, while atezolizumab did not improve the risk of recurrence either pre- or postoperatively. The chance of pregnancy was higher in younger patients attempting to conceive after breast cancer.