Surgery For Primary Breast Cancer Research Articles

Abstract PO5-09-01: Relative low body mass index (BMI) and fat quantity predicts prognosis better than absolute BMI in hormone receptor-positive, HER2-negative breast cancer

Abstract Purpose: Most existing research about obesity and prognosis in breast cancer patients primarily compares obese and non-obese individuals according to standard body mass index (BMI) categories. With a notably high percentage of Asian patients presenting with young age onset and normal weight, the prevalence of overweight and obesity based on absolute BMI values is lower in Asia (according to WHO guideline, BMI under 18.5 means underweight, and BMI over 25 means overweight). Understanding the impact of relatively low and high weight on prognosis can provide more insightful data than assessments based on absolute BMI thresholds. This study aimed to investigate the impact of relative low/high BMI on the prognosis of breast cancer and to explore the influence of body fat quantity (FQ), which is closely related to BMI. Methods: The study population consisted of 3,663 patients who received surgery for primary breast cancer at Seoul National University Hospital from 2006 to 2015. Pre-treatment BMI was divided into quartiles, defining low-BMI (Q1) as ≤ 21.33, high-BMI (Q4) as > 25.53, and mid-BMI as values between the two. Fat quantity (FQ) was derived from chest CT using the deep learning-based FDA-approved DeepCatch software. It measures the fat volume at the L1 level then divides this value by the square of the patient's height. It was then also divided into quartiles, establishing the definitions of low-, mid-, and high-FQ. The associations of BMI and FQ with distant metastasis-free survival (DMFS) and overall survival (OS) were examined. Results: The high-BMI group demonstrated older median age and higher T and N stages (p< 0.001). The high- and low-BMI groups also showed a higher prevalence of estrogen receptor positive cancer compared to the mid-BMI group. A strong correlation (Pearson correlation coefficient 0.83) was observed between BMI and FQ. In HR-positive, HER2-negative breast cancer, high-BMI patients had a 1.55 times higher risk of distant metastasis (95% CI: 1.15-2.11, p = 0.005), and a 1.78 times higher risk of mortality (95% CI: 1.22-2.58, p = 0.003) compared to mid-BMI patients, while low-BMI patients demonstrated better outcomes regarding DMFS (HR 0.67, p=0.035) and OS (HR 0.59, p=0.04). Comparison of FQ with prognosis revealed that the low-FQ patients exhibited better DMFS (HR 0.59, p=0.005) and OS (HR = 0.44, p=0.002) compared to mid-FQ patients in HR-positive, HER2-negative breast cancer. However, when adjusted for T and N stages, low-BMI patients in the HR-positive, HER2-negative group showed no difference in prognosis from mid-BMI patients but better prognosis compared to high-BMI patients. In contrast, when defined using absolute BMI, underweight patients did not show a difference in DMFS (HR 0.72 vs. normal BMI, p = 0.515) and OS (HR 0.91 vs. normal BMI, p = 0.87) compared to those with normal weight and overweight. The low-FQ group had the best prognosis regarding DMFS (HR 0.66 vs. mid-FQ, p=0.032) and OS (HR 0.50 vs. mid-FQ, p=0.008). Conclusions: Low-BMI is a favorable prognostic factor compared to high-BMI for DMFS and OS in HR-positive, HER2-negative breast cancer. The relative BMI defined according to BMI quartiles was a better prognostic factor than to absolute BMI standards. Investigations with FQ showed similar tendencies, suggesting that low BMI's favorable prognostic influence may be associated with fat. Future investigations should aim to validate these results and delve deeper into the underlying mechanisms. Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Soon Ho Yoon work as chief medical officer in MEDICALIP. This author did not involve data/statistical analysis. Other authors have no competing interest to declare. Citation Format: Eunhye Kang, Ji-Jung Jung, Ik Beom Shin, Hawjeong Lee, Jin Young Byeon, Changjin Lim, Hong-Kyu Kim, Hyeong-Gon Moon, Wonshik Han, Jong-Ho Cheun, Soon Ho Yoon, Han-Byoel Lee. Relative low body mass index (BMI) and fat quantity predicts prognosis better than absolute BMI in hormone receptor-positive, HER2-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 PO5-09-01.

Abstract TC-02: When to do a window trial

Abstract The window of opportunity in the short time between diagnosis and surgery for primary breast cancer has been exploited in trials of many endocrine agents. In these cases the therapeutic effect is antiproliferative and immunohistochemical detection of changes in Ki67 are considered a valid biomarker of likely long term efficacy. Trials have also been extended to assessment of inhibitors of growth factor receptors (eg lapatinib) and COX2 inhibitors. In these circumstances the mode of action is not purely inhibition of proliferation such that while changes in Ki67 may be of interest they should not be taken as necessarily reflecting the presence or absence of efficacy. It is also important to recognise that it may take longer than the time window available to get to a pharmacodynamic steady state. This is reflected by data from studies of tamoxifen and of GnRH analogues in premenopausal women. As well as being a window for assessing the biologic effectiveness of new agents it has been used as a means of assessing the prognosis of patients taking an established drug such as an aromatase inhibitor (AI) in the POETIC and an AI or tamoxifen in the ADAPT trial. Citation Format: M. Dowsett, S. Hurvitz. When to do a window 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 TC-02.

Abstract PO3-06-02: Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study

Abstract Background: Until 2012, breast cancer patients with micrometastases (pN1mi) or isolated tumor cells (pN0(i)) in the sentinel node (SN) received axillary lymph node dissection (ALND). ALND is associated with lymphedema, paresthesia, functional impairment, and pain. In 2012, national Danish guidelines for patients with pN1mi and pN0(i) were changed reflecting several randomized clinical trials showing non-inferior prognosis when ALND was omitted. Since 2012, appr. 450 Danish breast cancer patients have been spared ALND each year. Development of axillary recurrence(AR) from minimal metastatic disease left in the axilla may take longer than experienced after macrometastatic disease. Hence, long-term follow-up is needed to evaluate the safety of omitting ALND for patients with pN1mi and pN0(i). Therefore, we aimed to investigate these outcomes with 10 years of follow-up. Methods: In this national register-based study, we included all women with primary breast cancer surgery between 01.01.2008 and 31.12.2021, who had pN1mi and pN0(i) in the SN. Women treated between 01.01.2008-31.12.2011 had received ALND, while in women treated between 01.01.2012 and 31.12.202,1 ALND was omitted. The two groups were compared with SN-negative patients (pN0) without ALND. The primary outcome was AR, and the secondary outcome was overall survival (OS). Information on surgery, nodal status, and recurrence were retrieved from the national Danish breast cancer group (DBCG) database. The definitions of pN1mi, pN0(i) and pN0 were according to AJCC, 8TH edition. We analyzed patient- and tumor characteristics with descriptive statistics, χ2 and Fisher exact test. The cumulative incidence of AR was calculated. OS was estimated using the Kaplan-Meier method and compared with a log-rank test. The effect of ALND was estimated with a Cox proportional hazards model, adjusting for age at operation, histology, malignancy grade, hormone receptor, HER2 status, and whether they received adjuvant systemic treatment or radiation therapy. With all statistical analysis, a two-tailed α-level of 0.05 was used. Results: 22,790 patients were included in the study. Overall,14.3% had pN1mi, 8.6% had pN0(i) and 77.1% had pN0. Of pN1mi or pN0(i) patients, 1490 had an ALND; 1227 patients with pN1mi and 263 patients with pN0(i). In 3737 patients ALND was omitted: 2036 with pN1mi and 1701 with pN0(i). Regarding the primary outcome, 1.1% of patients with pN1mi or pN0(i) had an AR, while 0.5% of the pN0 patients had AR. Analyzing patients with pN1mi or pN0(i) with or without ALND, 0.2% and 1.5%, respectively, had an AR. In subanalysis of patients with pN1mi with or without ALND, 0.2% and 1.8%, respectively, had an AR. In a subanalysis of patients with pN0(i), no patients with pN0(i) and ALND had an AR, while 1.1% of patients with pN0(i) had an AR when ALND was omitted. OS after 10 years of follow-up for the group of patients with pN1mi or pN0(i) was 81.5%; 83.7% for patients with and 79.12% for patients without ALND. For pN0 patients without ALND OS was 82%. This difference between the three groups was statistically significant(p< 0,01). However, when adjusting for risk factors, there was no statistically significant difference in OS between the patients with pN1mi or pN0(i) with and without ALND (p=0.6). Likewise, no statistically significant difference was found in OS, when looking at the subgroups of pN1mi with or without ALND (p=0.5) and pN0(i) with and without ALND(p=0.41). Conclusion: In this large register-based nationwide study we found a slightly higher rate of AR after 10 years of follow-up in breast cancer patients with micrometastases or isolated tumor cells in the SN if ALND was omitted. However, the axillary recurrence rate was low (< 2%), and after adjusting for other risk factors the increased recurrence rate did not affect OS. These results confirm the safety of omitting ALND in these patients. Citation Format: Riazan Hawaz-ali, Frederikke Munck, Tove Tvedskov, Niels Kroman. Ten years axillary recurrence and survival after omission of axillary lymph node dissection in breast cancer patients with micrometastases or isolated tumor cells in the sentinel node: A Danish national register study [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 PO3-06-02.

Abstract PO4-01-09: The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) Breast Cancer

Abstract Backgrounds: We previously reported an analysis of the impact of adjuvant endocrine therapy (ET) for patients with ER+ and HER2- T1a/bN0M0 breast cancer (BC) at ASCO 2023 (Abstract #538). For the whole cohort, adjuvant ET significantly reduced distant metastases, but the absolute overall survival (OS) difference was small. The presence of medical comorbidities related to treatment toxicity and the estimated life-expectancy differ based on age, affecting the clinical impact of ET. There may be settings where comorbidities result in a sufficiently short, expected OS such that the benefit of ET will not outweigh risk. In multivariate analysis, age (<55 vs >55) was not an independent risk factor for distant metastasis. Here we evaluate the impact of adjuvant ET for ER+/HER2- T1a/bN0M0 breast cancer by age-specific subgroups, focusing on younger (< 40) and older (>65) population. Methods: This is a multicenter retrospective cohort study that evaluated the impact of adjuvant ET for patents with ER+/HER2- T1a/bN0M0 BC who underwent primary breast cancer surgery between 2008 and 2012 in 47 institutes of the Japan Clinical Oncology Group (JCOG). We analyzed distant metastatic-free survival (DMFS) and OS using Kaplan-Meier estimates with log-rank test in patients treated with and without ET in each of three age-specific subgroups (<40, 41-64 and 65> years of age). Results: Median follow-up was 9.2 years; the median age of the entire cohort was 55 years. Of 4756 eligible patients, 417 patients were age 65 (1025 (82%) with ET and 227 (18%) without ET). Of all 3989 (84%) patients with ET (2053 (51%) with Tamoxifen, 2142 (54%) with Aromatase inhibitor, 595 (15%) with LH-RH analog and 76 (2%) with others, includes duplicates). In the < 40 subgroup, 9-year DMFS was 97.2% with ET and 91.0% without ET (p=0.023) and 9-year OS was 97.8% with ET and 97.0% without ET (p=0.954). In the > 65 subgroup), 9-year DMFS was 92.6% with ET and 84.0% without ET (p< 0.01) and 9-year OS was 93.8% with ET and 84.9% without ET (p< 0.01). In those aged 41-64, no significant difference was observed in both 9-year DMFS and OS between patients with and without ET (p=0.328 and p=0.731, respectively) See Table for details. Conclusions: Adjuvant endocrine therapy was associated with improved distant metastatic-free survival in the younger (<40) and older (>65) population in this large Japanese dataset and was associated with improved overall survival in those >65. Our findings suggest clinically relevant benefit from ET in both younger and older unselected patients with very small ER+ BC. The lack of benefit in patients aged 41-64 is likely due to individual tumor and treatment factors, which will be evaluated and described in detail at the meeting. Table. The 9-year DMFS and OS of each age-specific three subgroups. *They are analyzed by using Kaplan-Meier estimates with log-rank test between patients treated with and without ET. Citation Format: Yuko Takahashi, Shinsuke Sasada, Naoto Kondo, Hiroya Hashimoto, Kaori Terata, Kumiko Kida, Yasuaki Sagara, Yoichi Naito, Keisei Anan, Takayuki Ueno, Akihiko Suto, Chizuko Kanbayashi, Mina Takahashi, Rikiya Nakamura, Toshiyuki Ishiba, Michiko Tsuneizumi, Seiichiro Nishimura, Yukinori Ozaki, Akihiko Shimomura, Takehiko Sakai, Tsuguo Iwatani, Hideo Shigematsu, Kenji Tamura, Tomomi Fujisawa, Takashi Hojo, Fumitaka Hara, Tadahiko Shien, Hiroji Iwata. The Prognostic Impact of Adjuvant Endocrine Therapy by Age for Patients with Small Estrogen Receptor-Positive (ER+), Human Epidermal Growth Factor 2 Negative (HER2-) 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 PO4-01-09.

Long-term oncologic outcomes of unselected triple-negative breast cancer patients according to BRCA1/2 mutations

Triple-negative breast cancer (TNBC) patients are more likely to have BRCA1/2 mutations, with a prevalence rate of about 10–20%. Although several studies have analyzed the oncologic outcomes between BRCA1/2 carriers and non-carriers, the impact on breast cancer patients is still unclear. A retrospective review was performed to determine the long-term outcomes of TNBC patients, focusing on the impact of BRCA1/2 mutations. A total of 953 TNBC patients who underwent primary breast cancer surgery from June 2008 to January 2016 were included. We examined long-term outcomes, including contralateral breast cancer (CBC) incidence, recurrence patterns, and survival rates over a median follow-up of 80.9 months (range 3–152 months). 122 patients (12.8%) had BRCA1/2 mutations. BRCA1/2 mutation carriers were significantly younger at diagnosis and more likely to have a family history of breast/ovarian cancer. CBC incidence at 60, 120, and 150 months was significantly higher in BRCA1/2 mutation carriers compared to non-carriers (P = 0.0250, 0.0063, and 0.0184, respectively). However, there were no significant differences in disease-free survival, overall survival, breast cancer-specific survival, or distant-metastasis-free survival between the two groups. BRCA1/2 mutation status was a significant risk factor for CBC (HR = 6.242, P < 0.0001). Interestingly, among 29 patients with CBC recurrence, 24 patients (82.8%) had recurring TNBC subtype and among the CBC recurrence patients, 19 patients (65.5%) resumed chemotherapy. In the TNBC subtype, appropriate genetic testing and counseling are pivotal for surgical decisions like risk-reducing mastectomy (RRM). Furthermore, long-term surveillance is warranted, especially in BRCA1/2 carriers who did not receive RRM.

Second Primary Breast Cancer in Young Breast Cancer Survivors

Among women diagnosed with primary breast cancer (BC) at or younger than age 40 years, prior data suggest that their risk of a second primary BC (SPBC) is higher than that of women who are older when they develop a first primary BC. To estimate cumulative incidence and characterize risk factors of SPBC among young patients with BC. Participants were enrolled in the Young Women's Breast Cancer Study, a prospective study of 1297 women aged 40 years or younger who were diagnosed with stage 0 to III BC from August 2006 to June 2015. Demographic, genetic testing, treatment, and outcome data were collected by patient surveys and medical record review. A time-to-event analysis was used to account for competing risks when determining cumulative incidence of SPBC, and Fine-Gray subdistribution hazard models were used to evaluate associations between clinical factors and SPBC risk. Data were analyzed from January to May 2023. The 5- and 10- year cumulative incidence of SPBC. In all, 685 women with stage 0 to III BC (mean [SD] age at primary BC diagnosis, 36 [4] years) who underwent unilateral mastectomy or lumpectomy as the primary surgery for BC were included in the analysis. Over a median (IQR) follow-up of 10.0 (7.4-12.1) years, 17 patients (2.5%) developed an SPBC; 2 of these patients had cancer in the ipsilateral breast after lumpectomy. The median (IQR) time from primary BC diagnosis to SPBC was 4.2 (3.3-5.6) years. Among 577 women who underwent genetic testing, the 10-year risk of SPBC was 2.2% for women who did not carry a pathogenic variant (12 of 544) and 8.9% for carriers of a pathogenic variant (3 of 33). In multivariate analyses, the risk of SPBC was higher among PV carriers vs noncarriers (subdistribution hazard ratio [sHR], 5.27; 95% CI, 1.43-19.43) and women with primary in situ BC vs invasive BC (sHR, 5.61; 95% CI, 1.52-20.70). Findings of this cohort study suggest that young BC survivors without a germline pathogenic variant have a low risk of developing a SPBC in the first 10 years after diagnosis. Findings from germline genetic testing may inform treatment decision-making and follow-up care considerations in this population.

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 &amp; 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 &amp; 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.

Neuropathic pain after surgery - A clinical validation study and assessment of accuracy measures of the 5-item NeuPPS scale.

The aim of this study was to validate the Neuropathic Pain for Post-Surgical Patients (NeuPPS) scale against clinically verified neuropathic pain (NP) by quantitative sensory testing (QST) as well as evaluation of other psychometric properties. The NeuPPS is a validated 5-item scale designed to evaluate NP in surgical populations. Data from 537 women aged >18 years scheduled for primary breast cancer surgery enrolled in a previous study for assessing risk factors for persistent pain after breast cancer treatment were used. Exclusion criteria were any other breast surgery or relevant comorbidity. A total of 448 eligible questionnaires were available at 6 months and 455 at 12 months. At 12 months, 290 patients completed a clinical examination and QST. NeuPPS and PainDETECT were analyzed against patients with and without clinically verified NP. NP was assessed using a standardized QST protocol including a clinical assessment. Furthermore, the NeuPPS and PainDETECT scores were psychometrically tested with an item response theory method, the Rasch analysis, to assess construct validity. Primary outcomes were the diagnostic accuracy measures for the NeuPPS, and secondary measures were psychometric analyses of the NeuPPS after 6 and 12 months. PainDETECT was also compared to clinically verified NP as well as NeuPPS comparing the stability of the estimates. Comparing the NeuPPS scores with verified NP using a receiver operating characteristic curve, the NeuPPS had an area under the curve of 0.80. Using a cutoff of 1, the NeuPPS had a sensitivity of 88% and a specificity of 59%, and using a cutoff of 3, the values were 35 and 96%, respectively. Analysis of the PainDETECT indicated that the used cutoffs may be inappropriate in a surgical population. The present study supports the validity of the NeuPPS as a screening tool for NP in a surgical population.

Impact of type 2 diabetes on complications after primary breast cancer surgery: Danish population-based cohort study.

Knowledge is sparse on the impact of type 2 diabetes (T2D) on surgical outcomes after breast cancer surgery. This study investigated the association between T2D and risk of complications after primary breast cancer surgery, and evaluated the biological interaction between T2D and co-morbidities. Using the Danish Breast Cancer Group clinical database, a cohort of all Danish women diagnosed with early-stage breast cancer during 1996-2022 was created. All patients underwent mastectomy or breast-conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries. Surgical complications were defined as hospital diagnoses for medical or surgical complications developing within 30 days after primary breast cancer surgery. The 30-day cumulative incidence proportion of complications was calculated, and Cox regression was used to estimate HRs. Interaction contrasts were computed to determine the additive interaction between T2D and co-morbidities on the incidence rate of complications. Among 98 589 women with breast cancer, 6332 (6.4%) had T2D at breast cancer surgery. Overall, 1038 (16.4%) and 9861 (10.7%) women with and without T2D developed surgical complications, yielding cumulative incidence proportions of 16 (95% c.i. 15 to 17) and 11 (10 to 11)% respectively, and a HR of 1.43 (95% c.i. 1.34 to 1.53). The incidence rate of surgical complications explained by the interaction of T2D with moderate and severe co-morbidity was 21 and 42%, respectively. Women with breast cancer and T2D had a higher risk of complications after primary breast cancer surgery than those without T2D. A synergistic effect of T2D and co-morbidity on surgical complications can explain this association.

Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer.

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Trainees as primary operators do not significantly impact perioperative complication rates in breast surgery

BackgroundThere is a trend for specialist care in breast surgery resulting in fewer primary operative cases for general surgery trainees; and subsequently that trainees performing advanced oncoplastic techniques in breast surgery may negatively impact patient morbidity. We have reviewed the complication rates between Australian general surgery trainees and Breast Consultants. MethodsA retrospective analysis was performed over a 5-year period (January 2016–December 2021). The key endpoints measured were relative complication rates for consultants compared to trainees, subdivided by surgery type. Surgeries were categorised as either benign, primary breast cancer surgery or re-excision. ResultsA total of 2646 operative cases were performed with the primary operator rate for consultants 58.35 % (n = 1544) and for trainees 41.65 %% (n = 1102). The overall complication rate was 2.83 % (n = 75); the overall rate for the consultants was 2.65 % and 3.08 % for the trainees. The complication rates were not statistically significant (p = 0.59) between the two groups. The mastectomy only complication rate was higher in the consultant group with a result of 7.3 % compared to 2.8 % for the trainees however was not statistically significant (p = 0.18). The most common complication was haematoma formation for both groups. ConclusionsThis study has demonstrated that trainees can safely perform advanced oncoplastic techniques without statistically elevated morbidity. In an era where breast surgery caseloads are increasing, but the exposure to breast surgery during training are decreasing, it is necessary to implement a practice where trainees can perform breast operations under supervision at a specialized unit.

Age-Related Incidence and Peak Occurrence of Contralateral Breast Cancer

ImportanceYoung patients with breast cancer have higher risk for developing contralateral breast cancer (CBC) and have epidemiologic characteristics different from those of older patients.ObjectiveTo examine the incidence and peak occurrence of CBC according to age at primary breast cancer (PBC) surgery.Design, Setting, and ParticipantsThis cohort study included patients who were diagnosed with and underwent surgery for unilateral nonmetastatic breast cancer at Asan Medical Center, Korea, between January 1, 1999, and December 31, 2013, with follow-up through December 31, 2018. Data were analyzed from December 1, 2021, through April 30, 2023. Patients were divided into 2 groups according to their age at surgery for PBC: younger (≤35 years) vs older (&amp;amp;gt;35 years).Main Outcomes and MeasuresThe main outcomes were cumulative incidence and hazard rate of CBC in the entire study population and in subgroups divided by cancer subtype, categorized according to hormone receptor (HR) and ERBB2 status.ResultsA total of 16 251 female patients with stage 0 to III breast cancer were analyzed; all patients were Korean. The mean (SD) age was 48.61 (10.06) years; 1318 patients (8.11%) were in the younger group, and 14 933 (91.89%) were in the older group. Median follow-up was 107 months (IQR, 79-145 months). Compared with the older group, the younger group had significantly higher incidence of CBC (10-year cumulative incidence, 7.1% vs 2.9%; P &amp;amp;lt; .001) and higher risk (hazard ratio, 2.10; 95% CI, 1.62-2.74) of developing CBC. The hazard rate, which indicates risk for developing CBC at a certain time frame, differed according to the subtype of primary cancer. In patients with the HR+/ERBB2– subtype, the risk increased continuously in both age groups. In patients with the triple negative subtype, the risk increased until approximately 10 years and then decreased in both age groups. Meanwhile, in the HR−/ERBB2+ subtype, risk peaked earlier, especially in the younger group (1.7 years since first surgery in the younger group and 4.8 years in the older group).Conclusions and RelevanceIn this cohort study, patients aged 35 years or younger with breast cancer had a higher risk of developing CBC than older patients. Moreover, young patients with the HR−/ERBB2+ subtype tended to have a shorter interval for developing CBC. These findings might be useful in guiding treatment decisions, such as contralateral prophylactic mastectomy.

Impact of Primary Breast Surgery on Overall Survival of Patients With De Novo Metastatic Breast Cancer: A Systematic Review and Meta-Analysis.

Breast surgery in cases of de novo metastatic breast cancer (MBC) is associated with improved outcomes in retrospective studies, although the results of randomized controlled trials (RCTs) are conflicting. We aimed to investigate whether surgery in this context prolongs patient survival. We performed a systematic review of the literature to identify RCTs comparing surgery of primary breast cancer to no surgery in patients with de novo MBC. Cochrane Library, Embase, Medline (OVID), and Web of Science were searched with latest update in July 2023, while conference proceedings were manually searched. Data concerning patient and tumor characteristics, as well as outcomes, were extracted. A meta-analysis with random effects models was performed considering heterogeneity between trials. Overall, 3255 entries were identified and 5 RCTs fulfilled all inclusion criteria, which had enrolled 1381 patients. The overall estimation in the intention-to-treat population showed no benefit for patients who had surgical excision of the primary breast tumor (HR = 0.93; 95% CI, 0.76-1.14). No subgroups in terms of receptor status or patterns of metastasis seemed to benefit from surgery, except for younger/premenopausal patients (HR = 0.74, 95% CI, 0.58-0.94). Breast surgery was associated with improved local progression-free survival (HR = 0.37, 95% CI, 0.19-0.74). Surgery of the primary tumor in patients with de novo MBC does not prolong survival, except possibly in younger/premenopausal patients. Breast surgery should be offered within the context of well-designed clinical trials examining the issue.

Oncoplastic breast conserving surgery versus standard breast conserving surgery for early and locally advanced breast cancer: a retrospective analysis from Sri Lanka

BackgroundBreast aesthetics is becoming increasingly important in breast cancer surgery due to changes in patient expectations and greater emphasis been placed on the psychosocial outcomes. Studies have shown no difference in local recurrence risk between mastectomy and breast conserving surgery (BCS) and also a higher overall survival rate after BCS. Breast preservation improves the quality of life substantially compared to mastectomy. Oncoplastic breast-conserving surgery (O-BCS) involves tumour excision whilst overcoming the limitations of standard breast conserving surgery (S-BCS) by allowing larger resection volumes, avoiding deformities with better aesthetic results. Our study aims to compare the oncosurgical and aesthetic outcomes of O-BCS versus S-BCS among women in Sri Lanka.MethodsWe conducted a retrospective study over a 4-year period including patients who underwent breast conservation surgery for primary non-metastatic breast cancer in two tertiary care units. We assessed outcomes in terms of re-excision rates, resection margin, complications and aesthetic outcomes using a Likert scale questionnaire to grade specific outcomes such as symmetry, volume, nipple position, scar visibility. Non-parametric tests were used for statistical analyses.ResultsFifty-four and seventy-three patients underwent S-BCS and O-BCS respectively. The median specimen volume and the maximum tumour diameter were significantly higher in O-BCS [160(range:65–220); 4.2(range: 1.2–5.2)] compared to S-BCS [65(range:45–86); 2.4(range: 1.0-2.6)]. The median closest tumour margin was 16 mm (range:4-25 mm) in O-BCS while 6 mm (range:<1 – 12 mm) in S-BCS (p = 0.01). Close (< 1 mm) and positive margins needing re-excision were seen mostly in S-BCS. Superior aesthetic outcomes with statistical significant difference were reported in the O-BCS compared to S-BCS group with better symmetry, volume, nipple position and scar visibility. The re-excision rates were significantly lower in O-BCS group. There was no significant difference in the operative time and complications while the aesthetic outcomes were significantly superior in OBCS.ConclusionsOverall, Level 2 perforator flap based reconstruction had superior aesthetic outcomes. O-BCS is safe and more aesthetically acceptable with no difference in oncological outcome and operative time. More consideration should be given to aesthetic parameters such as scar visibility, nipple position, breast volume and shape when considering the best surgical option for the patients.

Estimation of a Structural Equation Modeling of Quality of Life Mediated by Difficulty in Daily Life in Survivors of Breast Cancer.

The purpose of this study was to clarify the structural relationship of quality of life (QOL) in survivors of breast cancer, including difficulty in daily life and negative experiences in daily activities, as health-related indicators. Participants were survivors of breast cancer for more than 2 years after primary breast cancer surgery and belonged to self-help groups. The assessment used FACT-B (QOL), HADS (anxiety and depression), SOC (sense of coherence), WHODAS 2.0 (difficulties in daily life), and CAOD (negative experiences in daily activities). Bayesian structural equation modeling (BSEM) was performed to analyze the hypothesized model. If the causal model was significant, multiplication of the path coefficient from emotional distress (anxiety and depression) to QOL, and from SOC to emotional distress, was considered a direct effect on QOL, and from SOC to difficulty in daily life, from difficulty in daily life to negative experiences in daily activities, and from negative experiences in daily activities to anxiety and depression were considered indirect effects on QOL. The participants comprised 73 survivors of breast cancer. The goodness of fit of the model in the BSEM was satisfactory. The direct effect was 0.274, and the indirect effect was 0.164. An additional finding of this study is that coping with difficulty in daily life and negative experiences in daily activities related to QOL may improve QOL.

Oncoplastic breast surgery in older women with primary breast cancer: a systematic review.

Oncoplastic procedures allow excision of larger breast tumours, or unfavourable tumour/breast ratio lesions while achieving a good cosmetic outcome. This increases the pool of patients eligible for breast conservation over mastectomy, reducing the need for more extensive surgery in older women and potentially improving their quality of life. Nonetheless, studies to date suggest a poor uptake of oncoplastic breast surgery in the older group. This review aimed to establish whether a disparity in uptake of oncoplastic breast surgery exists between older and younger women, and to explore the underlying reasons for this. A literature search was conducted on 17 January 2022 using MEDLINE and Embase. Eligible studies comprised full-text articles of patients who underwent oncoplastic breast surgery for primary invasive breast cancer, and included those aged at least 65 years. Ten published studies were identified. One study was ranked as providing level 2 evidence, and the remainder were level 3. A total of 567 women underwent oncoplastic breast surgery for primary breast cancer, of whom only 61 (10.8 per cent) were aged 65 years or older. None of the studies directly compared younger with older women, or explored the underlying factors contributing to this discrepancy in uptake. This review has demonstrated a lower uptake of oncoplastic breast surgery in older compared with younger women. Given the increasing number of older women living with breast cancer who may be eligible for breast-conserving surgery, further research into this area is required.

Second primary breast cancer in young breast cancer survivors.

10503 Background: Prior data suggests that the risk of second primary breast cancer (SPBC) is higher among women diagnosed with primary breast cancer (BC) before age 40. There is evidence that risk differs by primary tumor characteristics, cancer treatments, and genetic predisposition. However, studies investigating risk of SPBC by clinical risk factors are often limited by low numbers of young women and lack of complete patient data, particularly regarding germline genetic risk. Methods: Using the Young Women’s BC Study (YWS), a prospective cohort of 1,302 women ≤40 years diagnosed with BC from 2006-2016, we sought to compare clinical and treatment characteristics among women who developed an SPBC vs. those who did not. The analytic cohort included women diagnosed with Stage 0-III BC who did not undergo bilateral mastectomy (N = 685). Demographics, genetic testing and results, clinical events, and treatment data were collected through self-report on baseline and follow-up surveys (every 6 months for 3 years, then annually). Detailed tumor and treatment information, confirmation of genetic testing results, and new and recurrent cancer events were obtained through regular and triggered medical record review. Univariate and multivariate Cox proportional hazards models were used to examine associations of age, race, genetic testing results, hormone receptor status, stage, and grade of primary tumor, and cancer treatments with SPBC. Participants were censored at the time of local recurrence, metastasis, death, or loss of follow-up. Results: At a median follow-up time of 9.9 years [inter-quartile range (IQR) = 6.6-12.0 y], 17 patients developed an SPBC (2.5%), in whom 3 occurred in the ipsilateral breast after lumpectomy as primary BC surgery. Median time from primary BC diagnosis to SPBC diagnosis was 4.2 years (IQR = 3.3-5.6 y). Compared to those who did not develop an SPBC, a greater percentage of women who developed an SPBC had in situ disease as their primary BC (24% v. 6%) and were of Ashkenazi descent (12% v. 5%). In the 577 women who had had genetic testing, 544 (94%) were non-carriers of pathogenic variants. Risk of SPBC was 2.2% (N = 12) in non-carriers and 9.1% (N = 3) in the 33 carriers. In Cox univariate analyses, carriers had a 4.1 times higher risk of SPBC compared to non-carriers (HR = 4.14, 95% confidence interval (CI) = 1.67-14.66, p = 0.03), and primary diagnosis with in situ BC was associated with a 5-fold increased risk of SPBC (HR = 5.02, 95% CI = 1.63-15.41, p = 0.005). Both factors remained strongly associated with SPBC when tested together in a multivariate model. Conclusions: This prospective study demonstrated a low risk of SPBC in the first 10 years after diagnosis of early BC in young women who are not germline pathogenic variant carriers. The finding that risk of SPBC was higher after in situ primary BC at a young age warrants further investigation. These findings have important implications for the treatment and follow-up care of young women with BC.

159P The impact of the extent of the type of primary breast cancer (BC) surgery from the analysis of historical Italian trials

Breast-conserving surgery (BCS) is the treatment of choice for women with early-stage BC. Several studies indicated a better outcome in patients undergoing BCS plus radiotherapy (RT) in comparison with mastectomy (MAST) +/- RT (PMID:33950173, 27344114). Indeed, in comparison with MAST, BCS reduces the extent of surgery, but the addition of radiotherapy (RT) makes it hard to understand whether the differences in outcome may be attributed to the extent of the surgery only. We performed a competing risks re-analysis in terms of dynamics and crude cumulative incidence (CCI), of distant recurrence free survival (DRFS) from two historical randomized clinical trials which of the Istituto Nazionale dei Tumori of Milan: the “Milan 1” trial (n = 701; 1973-1980, PMID:7015141) which compared MAST with BCS plus RT (BCS+RT) and the “Milan 3” trial (n = 567; 1987-1989, PMID: 8387637) which adopted the same surgical conservative approach with (BCS +RT) or without (BCS -RT) RT. Clinical features such as primary tumour size, axillary lymph node status (N) and menopausal status were considered. Concerning distant recurrence (DR) dynamics in Milan 1 trial, evidence of a different intensity of cause-specific hazard was found among subgroups related to surgery and lymph-node status (test of interaction effect: P=0.005), though with similar multi-peaked hazard patterns. Indeed, we observed that a MAST-related worse outcome is present in women with positive N (N+). Analysis of CCI reveals that, for the subgroup of N+ patients in Milan 3 trial, removal of RT from BCS (BCS -RT) results in 30% higher incidence of DR, comparable to the difference between MAST N+ and BCS+RT N+ patients in the Milan 1 trial. In this re-analysis of historical randomized clinical trials, we report that the worse outcome of MAST in comparison with BCS may be mainly attributed to higher extensive surgery and that the effect of the extent of the surgery without RT is mostly confined to patients with N+ BC. The effect of RT, as assessed by the re-analysis of Milan 3 trial, is likely related to a combined effect of the control of local recurrences, and the potential systemic effect of RT.

Abstract P3-03-10: The Impact of Type 2 Diabetes on Complications after Primary Breast Cancer Surgery: a Danish population-based cohort study

Abstract Introduction Type 2 diabetes (T2D) is associated with obesity and other comorbidities involving multiple organ systems, which may increase the risk of postsurgical complications. Knowledge is sparse on the impact of T2D on the postsurgical outcome after breast cancer (BC) surgery in primary BC. Objectives To investigate the association of T2D and risk of complications after primary BC surgery, and according to neoadjuvant chemotherapy. Methods Our cohort included all Danish women diagnosed with early-stage operable BC during 1996-2018 registered in the Danish Breast Cancer Group clinical database. All patients had primary surgical treatment—mastectomy or breast conserving surgery. Information on prevalent T2D was collected from Danish medical and prescription registries, defining T2D via diagnostic codes or redemption of ≥2 prescriptions for glucose-lowering drugs. We defined postoperative complications as hospital admissions for medical or surgical complications (re-operations (excluding seromas), bleeding, infection, thrombosis, kidney or arterial cardiovascular disease) up to 30 days after primary BC surgery. We calculated the 30-day cumulative incidence function (CIF) of postoperative complications and used Cox regression to estimate hazard ratios (HR) and associated 95% confidence intervals (95% CI) overall, and stratified by the receipt of neoadjuvant chemotherapy, adjusting for potential confounders. Results Among 84,491 women with operable BC, 4,669 (5.5%) had prevalent T2D at time of BC surgery. Overall, 800 (17.1%) and 8,621 (10.8%) of BC patients with and without T2D developed postoperative complications corresponding to CIFs of 17% (95%CI: 16% - 18%) and 11% (95%CI: 10% - 11%), respectively, and a HR of 1.44 (95%CI: 1.34-1.56). 173 (3.7%) BC patients with T2D and 2,805 (3.5%) without T2D received neoadjuvant chemotherapy. Among those who did not receive neoadjuvant chemotherapy, the CIFs of postoperative complications was 17% (95% CI: 16% - 18%) and 11% (95% CI: 10% - 11%) for women with and without T2D, respectively, with a corresponding HR of 1.42 (95% CI: 1.31-1.53). For those with and without T2D who received neoadjuvant chemotherapy, the CIFs were 24% (95% CI: 18% - 30%) and 10% (95% CI: 9% - 11%), respectively, and with a corresponding HR of 2.08 (95% CI: 1.49-2.91). Conclusion Among women with BC, prevalent T2D at the time of primary BC surgery increases the risk of postoperative complications. This excess risk is particularly pronounced among patients who undergo neoadjuvant chemotherapy. Citation Format: Kasper Kjærgaard, Jannik Wheler, Looket Dihge, Peer Christiansen, Signe Borgquist, Deirdre Cronin-Fenton. The Impact of Type 2 Diabetes on Complications after Primary Breast Cancer Surgery: a Danish population-based cohort study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-10.

Abstract P5-03-01: Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study

Abstract Background Triple-negative breast cancer (TNBC) is known to have a higher risk of early recurrence and relatively low risk of late recurrence compared to luminal type breast cancer. Among all subtypes of breast cancer, TNBC is more likely to have BRCA1/2 germline mutation which showed prevalence rate from about 10% to 20% in previous reports. To date, there are only few studies about the effect of BRCA1/2 mutations on the long-term oncologic prognosis in TNBC patients. We analyzed long-term oncologic outcome in unselected TNBC patients according to BRCA1/2 mutations in a comprehensive single institution. Methods Among 11,994 patients who underwent primary breast cancer surgery at Samsung Medical Center (SMC) between June 2008 and January 2016, 1,628 (13.6%) were TNBC patients. Of those, patients with inadequate and unavailable samples at SMC biobank and patients with follow-up duration less than 12 months and who had distant metastasis at presentation were excluded from the study, and 953 patients were enrolled. A retrospective study was conducted and BRCA1/2 genetic testing was done with SMC biobank samples through Next Generation Sequencing (NGS). Results Among 953 unselected TNBC patients, 122 patients (12.8%) had BRCA1/2 mutations: 91 (9.5%) were in BRCA1, and 32 (3.4%) were in BRCA2. One patient had both BRCA1/2 mutations. BRCA1/2 carriers were more likely to have personal history of ovarian cancer (9.0% vs. 0.5%, p &amp;lt; 0.0001), family history of breast cancer and/or ovarian cancer (40.2% vs. 9.4%, p &amp;lt; 0.0001), bilateral breast cancer (4.9% vs. 1.2%, p = 0.0105), and higher nuclear grade (86.0% vs. 74.0%, p = 0.0250). The median follow-up duration was 80.9 months. There were no significant differences in disease-free survival (DFS), distant metastasis-free survival (DMFS), overall survival (OS), and breast cancer-specific survival (BCSS) (p = 0.375, 0.268, 0.413, and 0.133, respectively) between BRCA1/2 carriers and non-carriers. However, BRCA1/2 carriers showed significantly worse contralateral breast cancer (CBC)-free survival than non-carriers (p &amp;lt; 0.0001). Sixty and 120-months cumulative recurrence rate were 18.5% and 31.2% for BRCA1/2 carriers versus 19.3% and 22.7% for non-carriers (p = 0.834 and 0.136, respectively). However, cumulative recurrence rate at 150 months showed absolute but not statistically significant difference between BRCA1/2 carriers and non-carriers (36.2% versus 23.5%, p = 0.080). Cumulative CBC recurrence rate on 60, 120- and 150-months estimates were 6.7%, 18.7% and 25.5% for BRCA1/2 carriers versus 1.1%, 2.7% and 5.2% for non-carriers which showed statistically meaningful difference (p = 0.025, 0.006 and 0.018, respectively). Sixty months, 120- and 150-months cumulative expire rate were 11.2%, 15.6% and 27.7% for BRCA1/2 carriers versus 14.3%, 20.7% and 20.7% for non-carriers (p = 0.319, 0.202 and 0.549, respectively). Discussion In this unselected cohort of patients with TNBC, we found 12.8% (122 patients among 953) prevalence of BRCA1/2 mutations. The median follow-up duration was 80.9 months. There was no significant difference in DFS, DMFS, OS and BCSS by BRCA1/2 mutation status in long-term follow up. However, BRCA1/2 carriers showed significantly worse CBC recurrence rate at 60, 120- and 150- months. And also, BRCA1/2 carriers had 12.7% higher risk of recurrence than non-carriers at 150 months, which was not statistically meaningful but showed absolute difference. Among patients with CBC recurrence, 41.3% (12 patients among 29) were BRCA1 carriers, over 85% had TNBC type of recurred CBC and approximately 80% underwent chemotherapy. In conclusion, we demonstrated that CBC recurrence risk is relatively high in TNBC patients with BRCA1 mutation and showed high chance to receive chemotherapy. Therefore, long-term follow up and appropriate genetic counseling, risk assessment should be done properly for BRCA1/2 mutation carriers in TNBC patients. Citation Format: Soo Yeon Chung, Jai Min Ryu, You Jin Jung, Yeon Jin Kim, Hye Jin Kim, Seok Jin Nam, Seok Won Kim, Jonghan Yu, Byung Joo Chae, Jeong Eon Lee, Se Kyung Lee, Sung-Won Kim, Eun Young Kim. Long-term oncologic outcome of unselected triple-negative breast cancer patients according to BRCA1/2 mutations: a comprehensive single institution study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-01.