Assessment of Surgical Approach and Overall Survival in Young Women With Breast Cancer

Background Breast cancer is relatively rare in women younger than 35 years of age, accounting for 2–4% of the total number of breast cancer cases diagnosed each year in western countries and the USA 1–3. However, the proportion of young age-onset breast cancer was much higher in the Asian population 3–6. Breast cancer at a young age has been reported to have a more aggressive biological behavior and to be associated with worse prognosis compared with the disease in older patients 5,7–17. Higher incidence of recurrence and risk of death were detected in younger patients, even when more aggressive therapies were administered 10–14. Neoadjuvant chemotherapy (NCT) has been considered the standard treatment for locally advanced breast cancer patients. In human epidermal growth factor receptor 2 (HER2)-positive and triple-negative tumors, achievement of a pathological complete response (pCR) after NCT was associated with better survival outcomes 18. In recent studies, young breast cancer patients were reported to obtain higher pCR rates compared with older counterparts 19,20. However, it remains unclear whether pCR is a predictor for better prognosis in young breast cancer patients. In this study, we aimed to investigate chemotherapy response and its relation with prognosis in young breast cancer patients (<35 years old) who were treated with NCT. Patients and methods Patients From January 2003 to December 2013, patients with operable or locally advanced breast cancer who were treated with NCT at the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were reviewed systemically. The inclusion criteria for the study were as follows: (i) 35 years or younger or 60 years or older; (ii) diagnosis of invasive carcinoma confirmed by core needle biopsy before NCT and the lymph node status was evaluated by fine needle aspiration of palpable lymph node if applicable; (iii) immunohistochemical examination for estrogen receptor (ER), progesterone receptor (PgR), and HER2 status using tumor specimens from core needle biopsy; (iv) newly diagnosed breast cancer patients; (v) combination of paclitaxel and carboplatin (PC) in patients with triple-negative breast cancer as NCT; for other patients, a combination of cyclophosphamide and epirubincin (CE) as NCT with postoperative paclitaxel, or epirubincin in combination with paclitaxel (ET) as NCT 21; (vi) adequate hematologic, hepatic, and renal functions. The exclusion criteria for the study were as follows: (a) stage IV disease, bilateral breast cancer, male breast cancer, and patients complicated with other malignancies; (b) patients who did not have complete clinical information or immunohistochemistry; (c) patients who were lost to follow-up immediately after treatment. This study was a retrospective observational research and patients' information was collected in the hospital database. There was no direct intervention in patients' treatment or care. Therefore, a patient's consent was not required. This study was approved by the Ethics Committee of Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Treatment Before the initiation of NCT, bilateral breast MRI or ultrasound, chest radiography, abdominal ultrasound, or computed tomography scans were performed to determine clinical stage. All patients were staged according to the 7th TNM (tumor–node–metastasis) staging system maintained by the American Joint Committee on Cancer (AJCC). All patients received NCT with CE, or ET, or PC regimens. CE-T regimen: cyclophosphamide 600 mg/m2 intravenously, day 1, and epirubicin 80 mg/m2 intravenously, day 1, q14d×4 cycles in NCT, followed by postoperative sequential paclitaxel 175 mg/m2 intravenously, day 1, q14d×4 cycles; ET regimen: epirubincin 75 mg/m2 intravenously, day 1, and paclitaxel 175 mg/m2 intravenously, day 2, q21d×4 cycles as NCT; and two cycles of ET regimen were repeated after surgery; PC regimen: paclitaxel 175 mg/m2 intravenously, day 1, and carboplatin area under the curve=5 intravenously, day 1, q21d×6 cycles as NCT. Mastectomy or breast-conserving surgery was performed within 1 month after the completion of NCT. Adjuvant radiotherapy was prescribed at the discretion of physicians mainly on the basis of the TNM stage before NCT, followed by endocrine therapy in cases with ER-positive or PgR-positive tumors. Trastuzumab was recommended in HER2-positive patients, but not compulsory. Efficacy evaluation Clinical efficacy was estimated every two cycles by clinical, mammographic, B-ultrasound examinations, and MRI according to Response Evaluation Criteria in Solid Tumors 1.1 criteria. Pathological efficacy was assessed by pathologic report after surgery and imaging data. Efficacy evaluation indicators included pCR, clinical complete response (CR), clinical partial response (PR), overall objective response rate (ORR=CR+PR), clinical progressive disease (PD), and clinical stable disease (SD). pCR was defined as no histological evidence of malignancies or only in-situ residuals in breast tissue after surgery, and complete disappearance of lymph node metastasis. CR was defined as disappearance of all known lesions. PR was defined as at least a 30% decrease in the sum of the largest diameters of target lesions. PD was defined as at least a 20% increase in the sum of the largest diameters of target lesions or new lesions detected. SD was defined as a reduction in the largest sum diameters of tumors by no more than 30% or an increase of no more than 20%. Patients with overall objective response rate received planned treatment and sequential surgery. Patients who fulfilled the criteria for SD or PD at the initial efficacy evaluation received surgery as soon as possible and were then treated with alternative postoperative regimens. Statistical analysis All data were analyzed using SPSS medical statistical software (version 15.0; SPSS Inc., Chicago, Illinois, USA). Disease-free survival (DFS) was defined as the period from the date of receiving NCT to the date of recurrence or metastasis or last follow-up; overall survival (OS) was defined as the period from the date of receiving NCT to the date of death for any cause or last follow-up. Both OS and DFS were analyzed using the Kaplan–Meier method. Comparisons of OS or DFS between groups were performed using the log-rank test. A two-tailed P value less than 0.05 was considered statistically significant. The χ2 or Fisher's exact test was performed to compare the clinicopathological variables and pCR rates between the subgroup of younger than 35 years of age and the subgroup of older than 60 years of age. Results Patient characteristics and treatment From January 2003 to December 2013, a total of 141 breast cancer patients were enrolled in this study and 74 (52.5%) of these patients were younger than 35 years old. As shown in Table 1, younger patients presented a tendency to have a tumor size of more than 5 cm (P=0.085), to have axillary positive nodes (P=0.118), and to have lymphovascular invasion (P=0.007) compared with their older counterparts (≥60 years old). As for the treatment, younger patients were more likely to choose breast-conserving surgeries (P=0.024) and to receive adjuvant radiotherapy after surgeries (P<0.001). For the entire cohort, the median number of NCT cycles was 4 (range: 4–6 cycles). The chemotherapy regimens were changed for a total of 31 patients who had a poor response to preoperative chemotherapies (including 26 SD and five PD). Overall, 52% (16/31) of these patients were in the young group, and the other 15 patients were older than 60 years. All 96 patients with preoperative or postoperative pathological ER-positive or PgR-positive breast cancer received different postoperative adjuvant endocrine therapies. In all, 18.9% (14/74) of patients in the young group and 16.4% (11/67) of patients in the old cohort received 1 year of trastuzumab after surgery or adjuvant chemotherapy.Table 1: Patients' baseline characteristicsTreatment response All patients were evaluable for response to NCT. The rates of pCR, clinical PR (except clinical PR, but confirmed as pCR finally), clinical SD, and clinical PD were 12.8% (18/141), 65.2% (92/141), 18.4% (26/141), and 3.5% (5/141), respectively. pCR rates were similar between the young group and the old cohort (12.2 vs. 13.4%, P=0.821). The PC regimen tended to yield higher pCR rates in the young cohort, but this was not statistically significant. HER2-positive or inflammatory breast cancer patients in young group were also more likely to achieve pCR compared with their older counterparts. As shown in Table 2, there were no significant differences between the pCR rates of young and old patients across various subgroup analyses, including hormone receptor status, axillary lymph node metastasis from primary tumors, primary tumor size, HER2 expression status, and NCT regimens.Table 2: Clinical and pathological factors affecting pathological complete response ratesSurvival analysis By the last follow-up on 1 November 2015, with a median follow-up of 32 months, 38 relapse events and 11 deaths have occurred. Patients in the young group showed significantly lower 5-year DFS compared with their old counterparts (Fig. 1a, 62.2 vs. 77.8%, P=0.037). However, no significant difference in 5-year OS was observed between the young group and the old cohorts (Fig. 1b, 84.0 vs. 94.8%, P=0.212).Fig. 1: (a) Kaplan–Meier curves of disease-free survival (DFS) in the young group (N=74) and the elderly group (N=67); Kaplan–Meier curves of overall survival (OS) in the young group (N=74) and the elderly group (N=67).In the group of young patients, pCR was not a significant predictor for DFS (Fig. 2a, P=0.408), whereas significant differences were observed with respect to the ascending TNM stage at diagnosis (Fig. 2b, P=0.001). In the subset of old patients, neither pCR nor TNM stage was a prognostic factor against DFS (Fig. 2c, P=0.129 and Fig. 2d, P=0.174).Fig. 2: Disease-free survival (DFS) curves by chemotherapy response (a) and TNM stage at diagnosis (b) in young patients; DFS curves by chemotherapy response (c) and TNM stage at diagnosis (d) in old patients. pCR, pathological complete response.To further explore the difference in survival between young and old groups, we carried out a stratified analysis. As shown in Fig. 3, the 5-year DFS was lower in the young group than in the old group within the subgroup of patients who presented with inflammatory breast cancer [56.5 vs. 75.1%, hazard ratio (HR)=2.47, P=0.044], with a large primary tumor (46.7 vs. 81.4%, HR=2.93, P=0.053), with lymph node involvement (57.7 vs. 74.8%, HR=2.40, P=0.025), and with higher TNM stage at diagnosis (46.7 vs. 67.1%, HR=2.52, P=0.027). Subgroup analyses on OS were carried out across predefined subsets and no significant difference was observed (Fig. 4).Fig. 3: Forest plot of disease-free survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Fig. 4: Forest plot of overall survival. Hazard ratio more than 1 indicated that old patients had better survival outcome. CI, confidence interval; ER, estrogen receptor; NA, not available; PgR, progesterone receptor; TNBC, triple-negative breast cancer.Discussion Although there was no consensus definition for young breast cancer, it had been widely believed that breast cancer at a young age had a more aggressive biological behavior compared with the disease arising from older patients. Tumors in younger women present with a higher grade, a higher T stage, a higher N stage, and more dedifferentiation, and have a higher proliferating fraction and more vascular invasion 5,7–17. In our study, the clinicopathological characteristics of young patients were consistent with previous researches. Keegan et al.22 and Colleoni et al. 23 found that higher proportions of HER2-positive tumors occurred in young patients. It was reported that about 25% of all breast cancers are ER or PgR negative, but a large proportion of hormone receptor-negative tumors occur in young women 13,15,17,24. Azim et al. 11 reported that there was a significantly higher proportion of basal-like tumors (34.3%) in young patients compared with those aged 41–52 (27.7%). No significant differences in the breast cancer subtype pattern were observed in this study and this could be attributed to the limited sample size of our study. It has been shown that younger age was associated with a less favorable prognosis 5,7–17. Tang et al. 15 found that with a follow-up of 54 months, inferior 5-year DFS (72 vs. 83%, P<0.01) and 5-year OS (87 vs. 93%, P <0.01) were observed in patients aged younger than 40 years compared with those aged 40–50 years. In our study, worse 5-year DFS was observed in young patients (62.2 vs. 77.8%, P=0.037), which was consistent with the results in previous studies. Stratified analysis showed that the predictive value of age on DFS was proven in the subgroup of patients with high-risk factors, including inflammatory breast cancer, large primary tumor, positive axillary lymph node, or higher TNM tumor stage at diagnosis, whereas no difference in the 5-year DFS was observed in patients without the above-mentioned risk factors. Similarly, in the study of Han et al. 5, there was no significant difference in DFS between young and old groups in lymph node-negative patients (P=0.223), whereas the younger group showed worse prognosis among lymph node-positive patients (P<0.001). In a Korean study, patients in the very young group with lymph node metastasis had poorer 5-year OS (70 vs. 83%, P<0.001) and DFS (58 vs. 74%, P <0.001) than their older counterparts; in patients without lymph node metastasis, the survival outcomes did not differ significantly between the two groups 17. Therefore, it is a key point to identify high-risk young breast cancer patients, and implement a tailored and aggressive treatment to improve the outcomes of these patients. It had been reported that improved survival outcomes were observed in patients with pCR compared with those with residual tumor 18,25–29. Further analysis showed that pCR was associated with better DFS in ER or PgR-positive/HER2-negative with grades 1–2, HER2-positive, and triple-negative disease, but not for those with ER or PgR-positive/HER2-positive, and ER or PgR-positive/HER2-negative with grade 3 tumors 18. In addition, in a meta-regression analysis of 29 heterogeneous neoadjuvant trials, pCR was not suggested to be a surrogate end point for DFS and OS in patients with breast cancer 30. At the 2016 annual meeting of American Society of Clinical Oncology, Robidoux et al. 31 reported 5-year outcomes of the NSABP protocol B-41 and found that long-term outcomes correlated with pCR status. Additional analyses indicated that pCR was related to a significant improvement in survival rates in the ER-negative subset, but not in the ER-positive cohort. In our study, young patients achieving pCR showed similar 5-year DFS compared with those with non-pCR (P=0.408). Therefore, pCR may be not an appropriate surrogate for prognosis in young breast cancer patients treated with NCT. The TNM staging system maintained by the AJCC is considered the most clinically useful cancer staging system for cancers. Orucevic et al. 32 reported on 782 Caucasian women diagnosed with invasive ductal carcinoma who were grouped according to TNM stage and molecular phenotype. The results supported the traditional TNM staging as a continued relevant predictive tool for breast cancer outcomes even with the emerging prognostic impact of tumor biomarkers (ER/PgR/HER2). Carey et al.33 suggested that classification of residual tumor in the breast and axillary surgical specimens after NCT using the AJCC TNM staging system could predict distant relapse and survival. In our study, young patients with higher TNM stage at diagnosis showed worse survival outcomes. Therefore, TNM stage may be more predictive of prognosis than pCR in breast cancer patients treated with NCT. This study is limited by its retrospective nature, nonrandomized design, small sample size, and relatively short follow-up duration. Trastuzumab was not covered by medical insurance in China and was much more expensive than common chemotherapy drugs. Therefore, some of the HER2-positive patients could not afford the expense. The diversity of NCT regimens and difference in the proportions of patients receiving trastuzumab between young and old cohorts may also have influenced the results of this study. Further prospective studies are warranted to validate the results. In recent years, researches have confirmed that breast cancer arising in young women is a unique disease entity driven by complex biologic processes extending beyond hormone receptors and hereditary cancer syndromes. Anders et al. 34 found 367 significant gene sets among young women's tumors that specifically distinguished them from tumors arising in older women, including those related to immune function, the mammalian target of rapamycin/rapamycin pathway, hypoxia, BRCA1, stem cells, apoptosis, histone deacetylase, and multiple oncogenic signaling pathways. In the study of Azim et al. 11, breast cancer in the young was enriched with processes related to immature mammary epithelial cells and growth factor signaling. There was also downregulation of apoptosis-related genes. The identification of genomic pathways specific to breast cancer arising in young patients provided a better understanding of the interplay of age and contributing biologic processes and a unique opportunity to explore therapeutic targets. Conclusion Young breast cancer patients treated with NCT present more aggressive clinicopathological features and worse prognosis compared with their elderly counterparts. TNM stage at diagnosis may be more predictive of prognosis than pCR in young breast cancer patients with NCT. The underlying biology of young breast cancer needs to be elucidated and the development of tailored treatment is crucial. Acknowledgements The authors thank all doctors and nurses of the Department of Medical Oncology for their help with the realization of this study. Binghe Xu and Jiayu Wang designed the research, analyzed the data, and wrote the paper; Jingjing Wang analyzed the data and wrote the paper; Jiayu Wang, Qing Li, Pin Zhang, Peng Yuan, Fei Ma, Yang Luo, Ruigang Cai, Ying Fan, Shanshan Chen, Qiao Li, Binghe Xu selected the cases and analyzed the clinical data. Conflicts of interest There are no conflicts of interest.

Clinicopathological features and prognoses of very young patients (≤35 years) with breast cancer: a retrospective population-based study in China.

1122 Background: Neoadjuvant chemotherapy is increasingly being used in the treatment of breast cancer, yet data on efficacy and significance of pathologic complete response (pCR) is limited among young women. We sought to determine whether timing of chemotherapy impacted disease-free (DFS) or overall survival (OS), and whether pCR is associated with improved prognosis among young women with breast cancer. Methods: We performed an IRB-approved review of women ≤40 years old who received treatment for stage I-III breast cancer during 1996-2008 at our institution. DFS and OS were determined through use of state tumor registry, death certificate data, and Social Security Master Death Index. Tumor biology was categorized as hormone receptor positive (HR+), HER-2+, or triple negative (TN) breast cancer. pCR was defined as lack of invasive cancer in the breast and axilla on final pathologic review. Cox regression analyses were conducted to evaluate the hazard ratios (HRs) of the association between chemotherapy and outcomes. Results: 370 women ≤40 years old (median age = 36.5, range: 22-40) were treated with systemic therapy for stage I-III breast cancer. 54.7% of tumors were HR+, 20.9% were HER-2+, and 24.4% were TN. After adjusting for stage, there was no difference in DFS or OS among women who received neoadjuvant versus adjuvant chemotherapy (p=0.6 and 0.5 respectively). pCR following neoadjuvant chemotherapy was higher among HER-2+ (50%) and TN (28.6%) tumors when compared to HR+ tumors (17.6%). Among women who received neoadjuvant chemotherapy, 10-year DFS and OS rates were significantly higher when pCR was achieved when compared to lack of pCR (HR=0.20, p value=0.01 and HR=0.13, p=0.05). pCR with neoadjuvant chemotherapy trended towards higher 10-year DFS and OS when compared to women who received adjuvant chemotherapy (HR=0.30, p value=0.08 and HR=0.20, p=0.1). Conclusions: pCR after neo-adjuvant chemotherapy is associated with improved disease-free and overall survival in young women with breast cancer. Pathologic complete response may be a valuable surrogate marker for survival, and aid in the evaluation of therapeutic efficacy in young breast cancer patients.

BMI is an independent prognostic factor for late outcome in patients diagnosed with early breast cancer: A landmark survival analysis

Abstract #6070 INTRODUCTION: Human epidermal growth factor receptor-2 (HER2) amplification has been associated with an aggressive breast cancer phenotype. The aims of this study were: 1) to determine if a relationship between HER2 amplification and local recurrence or overall survival (OS) existed; and 2) to compare prognostic effects of HER2 amplification with race, age, TNM stage, Scarff-Bloom-Richardson (SBR) grade, and hormone receptor status.&amp;#x2028; METHODS: Data were collected prospectively in our institutional review board approved breast center patient registry for patients with infiltrating ductal or infiltrating ductal-lobular mixed breast cancer; all other histologic types, including pure infiltrating lobular, were excluded from this analysis. Variables analyzed included race, age at diagnosis, tumor size, overall TNM stage, SBR grade, HER2 status, and hormone receptor status. Outcomes were defined as disease-free survival (local and distant) and OS. The prognostic effect of HER2 amplification on disease-free survival (DFS) and OS was assessed after adjusting for race, age, TNM stage, SBR grade, and hormone receptor status; Cox proportional hazards analysis was used in the multivariable analysis. A stepwise selection procedure was used in the multivariable analysis with p&amp;lt;0.10 required to allow a variable into the model and p&amp;lt;0.05 required to retain it in the final model. &amp;#x2028; RESULTS: Data were available for 1750 patients (mean age at diagnosis 60 years) diagnosed between January 2001 and July 2007; mean tumor size 1.8 cm, of which 384 (22%) were hormone receptor negative and 296 (17%) were HER2 amplified. Risk factors for DFS included HER2 amplification (Table 1), black race, increasing TNM stage, and negative hormone receptors. Risk factors for OS included black race, increasing TNM stage, and negative hormone receptors. HER2 amplification was associated with decreased disease-free survival (Fig 1a) but not OS (Fig 1b).&amp;#x2028; &amp;#x2028; &amp;#x2028; &amp;#x2028; CONCLUSIONS: Although HER2 amplification predicted disease-free survival, it did not predict OS in the multivariable analysis. A possible explanation for this finding is the increasing use of Trastuzumab for HER2 amplified tumors after relapse. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6070.

Retrospective Analysis of Risk Factors for Regional Recurrence for pN1 Patients After Breast Conserving Surgery

Multidisciplinary considerations in the treatment of triple-negative breast cancer.

Questions have existed as to whether residential segregation is a mediator of racial/ethnic disparities in breast cancer care and breast cancer mortality, or has a differential effect by race/ethnicity. Data from the Surveillance, Epidemiology, and End Results-Medicare database on white, black, and Hispanic women aged 66 to 85 years with breast cancer were examined for the receipt of adequate breast cancer care. Blacks were less likely than whites to receive adequate breast cancer care (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.71-0.86). Individuals, both black and white, who lived in areas with greater black segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.64-0.82). Black segregation was a mediator of the black/white disparity in breast cancer care, explaining 8.9% of the difference. After adjustment, adequate care for Hispanics did not significantly differ from whites, but individuals, both Hispanic and white, who lived in areas with greater Hispanic segregation were less likely to receive adequate breast cancer care (OR, 0.73; 95% CI, 0.61-0.89). Although Blacks experienced greater breast cancer mortality than whites, black segregation did not substantially mediate the black-white disparity in survival, and was not significantly associated with mortality (hazards ratio, 1.03; 95% CI, 0.87-1.21). Breast cancer mortality did not differ between Hispanics and whites. Among seniors, segregation mediates some of the black-white disparity in breast cancer care, but not mortality. Individuals who live in more segregated areas are less likely to receive adequate breast cancer care.

A Rosier Picture for Young Women With Breast Cancer.

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

Background: In the PENELOPEB trial, the addition of 1-year of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib to standard endocrine therapy (ET) for women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer at high risk of recurrence after neoadjuvant chemotherapy (NACT) did not improve invasive disease-free survival (iDFS) or overall survival (OS) in the main study analysis. Invasive lobular breast cancer (ILC) accounts for ~15% of all breast cancers (BC) and represents an underinvestigated subtype of BC with typically less sensitivity to (neo)adjuvant chemotherapy, and poor distant disease-free survival (DDFS) irrespective of response to NACT. Here, we report the post-hoc analysis results of iDFS, DDFS and OS in pre- and postmenopausal women enrolled on PENELOPEB and with ILC. Methods: Patients with HR+/HER2-negative BC without pathological complete response (pCR) after taxane-containing NACT and at high risk of relapse (CPS-EG score ≥3, or 2 and ypN+) were randomized (1:1) to receive 13 cycles of palbociclib 125mg daily or placebo on days 1-21 of a 28-day cycle in addition to standard ET with tamoxifen (TAM) +/- gonadotropin-releasing hormone analogue (GnRHa) or aromatase inhibitor (AI) +/- GnRH. Randomization was stratified by nodal status at surgery, age at first diagnosis (&amp;lt; 50 vs. ≥50 years), Ki-67, region, and CPS-EG score. ILC diagnosis was locally assessed and reported by the investigators on the pathology case report form. The primary objective of this post-hoc analysis was to evaluate iDFS, DDFS and OS by treatment arm in patients with high risk ILC. Results: A total of 1,250 patients were randomized, of whom 110 had ILC and were nearly uniformly distributed between both treatment arms (palbociclib n=58 vs. placebo n=52), with a higher proportion of postmenopausal women (58.6% in the palbociclib arm vs. 53.8% in the placebo arm) compared to premenopausal women (41.4% in the palbociclib arm vs. 46.2% in placebo arm). There was no difference in the distribution of AI/TAM use between the treatment arms. An estimated absolute 3-year-iDFS difference of 18.3% with palbociclib compared to placebo (iDFS 88.4% [95% CI 76.0-94.6] vs. 70.1% [95% CI 55.3-80.7]) with a HR of 0.66 [95% CI 0.27 – 1.61, log-rank p=0.354]) was observed. A comparable 3-year-DDFS difference of 16.3% was observed. An estimated 3-year-OS difference of 16.4% (98.0% [95% CI 86.6 – 99.7] vs. 81.6% [95% CI 67.5 – 90.0]) with a hazard ratio (HR) of 0.27 (95% CI 0.05 – 1.43, log-rank p=0.108) was observed. Out of 12 observed deaths (n=2 palbociclib vs. n=10 placebo), 11 (in placebo arm) were related to metastasic BC. Conclusions: In this post-hoc analysis, a trend towards improvement in OS and a trend in favor of iDFS and DDFS for the addition of palbociclib to ET was observed among women with HR+/HER2- ILC at high risk of recurrence after NACT, but these differences were not statistically significant. This could represent a valuable treatment option for patients with high risk ILC. Due to the small sample size of the ILC subgroup, further follow-up evaluation is necessary. Moreover, analyses in the ILC subgroup from other adjuvant CDK4/6 inhibitor trials could substantiate these findings. Table. Overall survival and disease recurrence rates in patients with invasive lobular breast cancer of the PenelopeB cohort Results of iDFS, DDFS and OS. Citation Format: Hervé Bonnefoi, Frederik Marmé, Miguel Martín, Michael Untch, Sung-Bae Kim, Harry Bear, Nicole McCarthy, Karen Gelmon, José Ángel García-Sáenz, Catherine M. Kelly, Toralf Reimer, Zhe Zhang, Masakazu Toi, Hope Rugo, Michael Gnant, Andreas Makris, Nader Hirmas, Valentina Nekljudova, Johannes Holtschmidt, Sibylle Loibl. Overall survival and disease recurrence rates in patients with invasive lobular breast cancer of the PenelopeB 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 PO4-02-04.

Technical Challenges of Heart Avoidance for Synchronous Breast and Lung Cancers in a Postmenopausal Female: A Planning Case Report From a Safety-Net Hospital

Randomized, controlled trials comparing breast-conserving therapy (BCT) with mastectomy have demonstrated equivalent overall survival (OS), but recent observational studies have shown improved OS in patients undergoing BCT. These studies provide limited data on young patients who are traditionally offered mastectomy due to perceived higher disease risk. This study examines the OS in a contemporary series of young women with breast cancer undergoing upfront BCT compared with mastectomy. Women ≤40 years old with primary invasive T1-T2, N0-N1 breast cancer were identified from the National Cancer Database between 2006 and 2016. Patient cohorts were based according to locoregional treatment: BCT, mastectomy alone (Mx), and mastectomy with radiotherapy (Mx/RT). Kaplan-Meier method followed by Cox proportional-hazards regression with inverse probability of treatment weighting (IPTW) were performed to account for treatment selection bias effects in OS. A total of 15,611 patients met the study criteria; 9,509 patients (60.9%) had BCT, 4,020 (25.8%) had Mx/RT, and 2,082 (13.3%) had Mx alone. The median follow-up was 4.6 years (interquartile range [IQR] 3.0-6.4). After IPTW-adjustment, the 5-year OS was similar for BCT (95%), Mx (95%), and Mx/RT (94%), and there was no significant difference in OS in Mx (hazard ratio [HR] = 1.16, 95% confidence interval [CI] 0.90-1.51) and Mx/RT (HR = 1.08, 95% CI 0.88-1.34) compared with BCT. Mx/RT was associated with decreased survival in patients with pT2N0 (HR = 1.78, 95% CI 1.12-2.84). Among young patients with early-stage breast cancer, overall survival was equivalent regardless of surgical approach. Breast-conserving therapy remains a safe option in young women despite the clinical tendency to offer upfront mastectomy in young patients.

Overall survival according to type of surgery in young (≤40 years) early breast cancer patients: A systematic meta-analysis comparing breast-conserving surgery versus mastectomy

A recent study found that in women with stage I or II breast cancer, breast-conserving therapy (BCT) was associated with improved disease-specific survival compared with mastectomy (Cancer. 2013;119:1402-1411). It has been believed for years that these 2 approaches to the locoregional treatment of early breast cancer are equivalent, and thus the percentage of women choosing BCT has increased. However, for unclear reasons, mastectomy is being chosen more often among certain groups of patients such as younger women, those with in situ cancer, and those living in more affluent areas (J Clin Oncol. 2010;28:e155-e157). Researchers set out to investigate whether the similar survival rates of BCT and mastectomy noted in randomized trials hold true for the general population, and to determine whether there is a subgroup that benefits from one approach versus the other. “In this observational study of over 112,000 women treated with early-stage breast cancer, women undergoing lumpectomy and radiation had equivalent, and in some subgroups superior, breast cancer-specific survival compared to women undergoing mastectomy,” says E. Shelley Hwang, MD, MPH, chief of breast surgery at Duke University Medical Center in Durham, North Carolina. Dr. Hwang and her colleagues identified cases of stage I or II breast cancer from the California Cancer Registry for patients diagnosed between 1990 and 2004. Women who were treated with either a lumpectomy followed by radiation therapy or mastectomy were eligible; women who had undergone a lumpectomy without radiation or a mastectomy with radiation were excluded. Overall, a total of 112,154 eligible women were found: 55% underwent BCT and 45% underwent mastectomy. The median follow-up was close to 10 years. BCT rates increased from 37% between 1990 and 1992 to 62% between 2002 and 2004. The 5-year overall survival (OS) rate of the entire cohort was 89.3%, and the disease-specific survival (DSS) rate was 94.4%. Cox multivariate analysis was performed to compare survival between 4 groups: 1) those aged 50 years or older with hormone receptor (HR)-negative disease; 2) those aged 50 years or older with HR-positive disease; 3) those aged younger than 50 years with HR-negative disease; and 4) those aged younger than 50 years with HR-positive disease. Human epidermal growth factor receptor 2 (HER2) status was not considered, as it was not widely available during the study period. In all the groups, BCT was associated with improved OS compared with mastectomy. The largest benefit was observed in the group of women aged older than 50 years who had HR-positive disease (hazard ratio, 0.81). The DSS benefit was also most prominent in this group, with a hazard ratio of 0.87. The smallest benefit for BCT was noted in the women aged younger than 50 years with HR-positive tumors (hazard ratio, 0.93). A large observational study recently compared outcomes of mastectomy and breast conserving therapy among women with early stage breast cancer. After adjusting for tumor grade, percentage of positive lymph nodes, race, socioeconomic status, tumor size, age at diagnosis, and year of diagnosis, the women treated with BCT still had significantly higher OS and DSS rates. Analysis was performed to examine whether comorbidities had an effect on surgical choice and outcomes. Heart disease, chronic respiratory disease, and cerebrovascular disease were considered. BCT was associated with significantly lower 3-year mortality rates from all causes, except for breast cancer. Kaplan-Meier survival estimates demonstrated statistically significantly increased OS and DSS for BCT versus mastectomy. In this analysis, the increased survival advantage of BCT was again found to be greatest among women aged 50 years and older with HR-positive disease. When examining the tumor size and surgical approach used, the survival benefit was larger among patients with T1 tumors compared with those with T2 tumors in all groups, but OS was still better in the BCT group among women with T2 tumors. Dr. Hwang and her colleagues state that the strengths of this study include a large, diverse population-based data set representing the state of California; a lengthy follow-up period; excellent reliability of data; and a more modern cohort than the randomized controlled trials comparing lumpectomy and mastectomy that were conducted over 30 years ago. However, the study was observational, and therefore the groups were not randomized. Researchers tried to control for all major factors known to impact breast cancer-specific survival, but there could be some unmeasured confounders associated with the choice of mastectomy that were not accounted for in the analysis and thus not controlled for in the study. In addition, the authors caution that as an observational study, causality could not be inferred. “This study by Hwang and colleagues shows there is no benefit of mastectomy measured in risk of local recurrence or survival,” says Stephen Edge MD, chief of breast surgery at Roswell Park Cancer Institute in Buffalo, New York. “Their findings that survival is better with BCT must be interpreted with caution as this was not a randomized trial. My review suggests that decisions they made in defining the study population and other methodologic issues could have biased the results towards a benefit from BCT where that benefit may or may not exist, a significant problem using population data. However, they clearly showed no worse outcome with BCT, thereby reaffirming the unequivocal findings from randomized controlled clinical trials with mature follow-up.” Since there are no data, including this study, that show mastectomy to be superior to BCT, it is interesting that there has been a recently reported trend showing an increased uptake of mastectomy over BCT by women with early-stage breast cancer. “The reasons underlying this trend are doubtless multifactorial; these include better breast reconstruction techniques, increased use of MRI, and increased awareness of breast cancer and its consequences. However, the trend is particularly fascinating because the segment of the population opting for more surgery—not only mastectomy, but bilateral mastectomy—are generally younger, more educated women with better access to health care and smaller, earlier cancers. This indicates that greater overall health literacy is associated with more surgery, despite the lack of evidence that supports better outcome with more surgery,” says Dr. Hwang. Dr. Edge agrees that for unknown reasons some women are asking for, and their surgeons are performing, more mastectomies. “Contributing factors include misinformation leading to fear. This is an area where thoughtful patient support is needed. Surgery is not a good treatment for unfounded fears,” he says. Future research could include examining the relationship between HER2 status and surgery and outcomes. Because these data have been recorded in the California Cancer Registry since 2006, this analysis should be possible. “This study points to the importance of large data sets and how they can be used to look at questions for which further randomized studies are not appropriate,” says Dr. Hwang. “Of course, there will always be cases in which a mastectomy is a better option, but for most women who have the choice, doing less may be more.”