Early Stage Breast Cancer In Women Research Articles

Abstract PO3-02-06: Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers

Abstract Introduction: In 2004 the CALGB 9343 study reported that women >70 years of age with pT1NO hormone receptor positive breast cancer received no meaningful benefit from breast irradiation following lumpectomy. Although there was a modest reduction in local recurrence, there was no improvement in rates of mastectomy for local recurrence, distant metastases, 5-year overall survival (OS) and breast cancer specific survival therefore concluding that it was reasonable to omit radiation therapy in this group. An update of the CALGB 9343 study in 2013 with 10-year follow-up came to the same conclusion. Previous analysis of the National Cancer Database (NCDB) and the SEER database showed, however, that the majority of women with these characteristics were still receiving radiation therapy. We conducted this retrospective analysis from NCDB to identify factors associated with the use of radiation in this population. Methods: We reviewed the NCDB database and collected records of all breast cancer patients aged >70 years, who had hormone positive (HR+), pT1N0 disease between the years of 2004-2019. They were separated into radiation and non-radiation cohorts and then stratified based on ethnicity, age groups, insurance status, income quartiles, education quartiles, areas of residence, tumor size, comorbidities, diagnosis to treatment time, treatment facility type and geographic location. We then compared mortality between the two cohorts and completed a multivariate analysis to determine the demographic and clinical factors associated with the likelihood of receiving radiation. SAS was used for analysis and p-value < 0.05 was deemed as statistically significant. Results: 147,611 patients met the criteria of age > 70, pT1N0, HR+ treated with surgical lumpectomy. The majority of them were white, aged 70-75y, had Medicare, were in higher education and income quartiles and lived in metro areas (Table 1). 57.9% of the total study population received radiation. The possibility of receiving radiation decreased as age increased beyond 75 years. Uninsured patients, Medicare patients, those with comorbities, higher educational status as well as those who lived 20+ miles away from their treatment facility and treated at urban centers in central or south Atlantic areas were less likely to receive radiation. Those treated at Comprehensive community cancer programs and middle Atlantic areas were more likely to receive radiation. The possibility of radiation also progressively increased with tumor size. However, there were no differences observed when stratified by race, income status or chemotherapy use (Table 2). We also noted a small overall survival advantage for the radiation cohort (HR 0.77, p-value < 0.0001) which could be explained by the fact that patients without comorbidities were more likely to receive radiation. Discussion: Our results provide a real-world estimate of radiation use in pT1N0 HR+ early-stage breast cancer in women > 70 years. The major predictors of radiation use included younger age, low co-morbidities, insurance and institutions providing care. Lack of awareness about recent updates or concern about local recurrence could be contributing to the continued use of radiation. Although there are minor differences when stratified by demographics, it is concerning that the overall trend of radiation use has not significantly decreased over time. Since there is currently no data to support the routine use of radiation in this patient group as evidenced by randomized controlled trials, it is prudent to avoid radiation. This approach would help reduce healthcare costs, patient inconvenience and associated morbidity. Table 1 Baseline characteristics Table 2 Factors affecting radiation use Citation Format: Suma Sri Chennapragada, Runhua Shi, Shivani Sharma, Gary Burton. Predictive Factors for adjuvant radiation use in patients >70 years with pT1N0 HR+ breast cancers [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 PO3-02-06.

Detection of early-stage breast cancer in women by plasma lipidomic profiling.

554 Background: Early detection of breast cancer provides the best opportunity for cure. Mammography is the benchmark for screening, but suffers technical, logistic, and diagnostic limitations. An effective and accurate blood test to detect early stages of the disease should increase the screening detection rate for breast cancer. We conducted a series of lipidomic studies in early-stage breast cancer patients and combined the datasets via a machine learning driven analysis to test if plasma lipidomic profiles can detect breast cancer. Methods: Blood samples were collected from women with stage 0-IV breast cancer (4 separate cohorts) with age and BMI matched breast cancer-free controls. Lipids from plasma enriched extracellular vesicles were extracted and analysed by high resolution accurate mass LC-MS. A commercially available software was used to annotate and quantify >400 manually curated lipid species. Following variable selection, a lipid signature was identified capable of distinguishing breast cancer samples from control. Results: Plasma samples from women with breast cancer were distinguished from controls with an average cross-validated accuracy of 0.81, and average AUC of 0.84 across 4 cohorts (Table 1). An optimised cross-cohort subset of early-stage IDC, DCIS and ILC were differentiated from controls with a cross-validated AUC of 0.90, sensitivity of 0.88 and specificity of 0.82 (201 early-stage breast cancer, 199 controls) (Table 1). For this optimised cohort our test achieved a sensitivity of 0.71 at a prescribed specificity of 0.90, or equivalently a sensitivity of 0.89 at a prescribed specificity of 0.80. Conclusions: Our study demonstrates the high sensitivity and specificity of a lipid biomarker signature with potential for early detection of breast cancer. Ongoing studies will prospectively compare the lipid-biomarker based test against mammographic and pathological diagnosis. [Table: see text]

Abstract P3-19-25: ICE3 trial - Radiation following cryoablation for low-risk breast tumors: Assessment of safety and variables that effect referral

Abstract Objectives. The ICE3 Trial is a study aimed to evaluate safety and efficacy of cryoablation in low-risk early-stage breast cancer in women ≥60 years. ICE3 Trial enrolled patients from 2014 through February 2019. In total, 206 females underwent cryoablation: however, 3 received treatment that was off protocol and 9 were excluded due to inclusion criteria. Of the 194 patients remaining, 27 had adjuvant radiotherapy. We aimed to examine treatment decisions regarding radiation referral and evaluate safety of the combined modalities in this population. Methods. The ICE3 study is a multi-center, single arm, non-randomized controlled clinical trial with 19 US sites. Data regarding factors that may affect recommendation for adjuvant radiotherapy was evaluated, including the patients' age, ethnicity, tumor characteristics and the treatment center location. We evaluated patient factors that might affect adverse events (AEs) including BMI, nicotine use, diabetes mellitus, as well as adjuvant therapy received. Results. All patients had early-stage breast cancer, 188 were Luminal A (96.9%), 194 were Her-2 negative (100%), 194 were ER positive (100%), 181 were PR positive (93.3%), 98 were Nottingham score 1 (50.5%) and the reminder (96) were Nottingham score 2 (49.5%). Overall mean age was 75.32 years (SD= 7.01), 70.81 years for the radiated group (n=27, SD=6.48) and 76.05 years (n=167, SD=6.83) for the non-radiated group respectively. We evaluated the number and percentage of patient’s receiving radiation at each center as a substitute for referral pattern at the centers. In the entire cohort, 27 of 194 patients (13.32%) underwent radiotherapy. We observed a wide range of variability between the centers (0%-60%) of patients underwent radiotherapy). The age of patient (P-value=0.0006) and the center (P-value=0.0009) were the only factors that appeared to influence if the patient received adjuvant radiation. In all but one center, the mean age of patients who received radiotherapy was lower than those who did not. Other factors including ethnicity, Nottingham score, tumor borders, tumor size, depth and shape did not impact the decision to offer radiation. Regarding safety evaluation, we compared factors leading to device-related AEs between radiated and non-radiated groups. In the total cohort, 21 of 194 patients had mild AEs (10.8%). In the radiated group, 5 AEs occurred in 3 of 27 patients (11.1%). AEs were classified as mild and included injection site pain, bruising, localized edema and breast infection. In the non-radiated group, 36 AEs occurred in 18 of 167 patients (10.8%). AEs were classified as non-serious; 31 were mild and 5 were moderate and included pain, bruising, hemorrhage, rash, induration and thermal injury. We also considered other factors such as age, adjuvant therapy, BMI, nicotine use and whether the patient had diabetes mellitus. No statistically significant factor was observed to effect AE. Conclusions. Cryoablation in the ICE3 trial was used as a replacement for surgical resection in patients with low-risk breast tumors. Many of these patients were elderly and could avoid radiation based on data from CALGB 93431. Still, 13.32% of patients received radiation and contributing factors seem to be patient’s age and referral practice of the treatment center. AEs in the cohort were infrequent and typically minor, and there was no difference between the radiated and nonradiated groups. Radiation in the setting of cryoablation is safe with minimal short-term side effects. 1Lumpectomy plus tamoxifen with or without irradiation in women age 70 years or older with early breast cancer: long-term follow-up of CALGB 9343.Hughes KS, Schnaper LA, Bellon JR, Cirrincione CT, Berry DA, McCormick B, Muss HB, Smith BL, Hudis CA, Winer EP, Wood WCJ Clin Oncol. 2013 Jul 1; 31(19):2382-7. Citation Format: Jill R Dietz, Richard E Fine, Susan K Boolbol, Roni Haziza. ICE3 trial - Radiation following cryoablation for low-risk breast tumors: Assessment of safety and variables that effect referral [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-19-25.

Association of Bone Metastasis With Early-Stage Breast Cancer in Women With and Without Precancer Osteoporosis According to Osteoporosis Therapy Status

Deaths from cancer are attributed more to secondary than primary tumors, but the pathogenesis of organ-specific cancer metastasis has not been determined. To investigate whether precancer osteoporosis and osteoporosis therapy are associated with alteration of bone metastasis patterns. This nationwide retrospective cohort study was performed from January 1, 2002, to December 31, 2013, using 2 cohorts from the Taiwan National Health Insurance Research Database: a random sample of 1 million beneficiaries from the Longitudinal Health Insurance Database who were enrolled in 2005 (LHID2005) and a specific data set of all the patients with osteoporosis. Patients diagnosed with breast cancer and precancer osteoporosis from January 1, 2002, to December 31, 2011, were included in the study, and their records were examined through December 31, 2013. From LHID2005, we selected 9104 women with early-stage breast cancer, of whom 705 had precancer osteoporosis. We identified 29 183 patients from the cohort of patients with breast cancer and osteoporosis, 14 020 of whom had precancer osteoporosis. Data analysis was performed from December 31, 2016, to August 31, 2018. Precancer osteoporosis and osteoporosis therapy. The risk of bone metastasis in patients with and without precancer osteoporosis and patients receiving and not receiving osteoporosis therapy as well as time to bone metastasis development. Among 9104 patients with breast cancer from the Longitudinal Health Insurance Database (mean [SD] age, 46.7 [14.0] years), precancer osteoporosis was not associated with a difference in risk of bone metastasis (adjusted hazard ratio [aHR], 0.87; 95% CI, 0.58-1.30; P = .49). Among 14 020 patients with precancer osteoporosis from the other cohort (mean [SD] age, 58.9 [11.6] years), osteoporosis therapy had no association with the risk of bone metastasis (bisphosphonates: aHR, 1.47; 95% CI, 1.00-2.17; P = .05; nonbisphosphonate drugs: aHR, 1.00; 95% CI, 0.72-1.39; P > .99). Compared with those without precancer osteoporosis (median time to bone metastasis development, 2.87 years; interquartile range [IQR], 1.34-4.86 years), among those with precancer osteoporosis, the median time to develop bone metastasis was shorter in those who did not receive treatment (1.74 years; IQR, 0.58-3.60 years; P < .001), whereas this time was the same for those who received treatment (bisphosphonates: 2.34 years; IQR, 1.23-3.13 years; nonbisphosphonate drugs: 2.08 years; IQR, 0.92-4.95 years). Precancer osteoporosis was not associated with risk of bone metastasis, but untreated osteoporosis was associated with accelerated progression of bone metastasis when it occurred. Organ microenvironments interact with disseminated cancer mostly after the specific organ has been predetermined to be the designated location. Because recurrences and metastases are major obstacles to cancer treatments, determining which organs may be at risk for metastases may be crucial to treating the disease.

Triptorelin: A Review of its Use as an Adjuvant Anticancer Therapy in Early Breast Cancer.

A 1-month formulation of the gonadotrophin-releasing hormone agonist (GnRHa) triptorelin (Decapeptyl®) has been approved in the EU as an adjuvant treatment in combination with tamoxifen or an aromatase inhibitor (AI), of endocrine-responsive, early-stage breast cancer in women at high risk of recurrence who are confirmed as premenopausal after completion of chemotherapy. This indication reflects the results of the 5-year SOFT and TEXT studies, especially SOFT, in which ovarian function suppression (OFS; mainly achieved with triptorelin) added to tamoxifen provided a significant benefit in the overall study population of premenopausal patients only after adjusting for prognostic factors. It emerged that adding OFS to tamoxifen produced more pronounced benefits in terms of disease control and, furthermore, increased overall survival in the cohort of higher-risk patients who had previously received chemotherapy. Also, compared with tamoxifen alone, the combination of OFS plus exemestane produced more pronounced benefits in terms of disease control than OFS plus tamoxifen. OFS induces premature menopause; when combined with either tamoxifen or exemestane, it increased the endocrine symptom burden. Nonetheless, the two combinations had distinct tolerability profiles (e.g. vasomotor symptoms and thromboembolic events were more frequent with OFS plus tamoxifen, whereas musculoskeletal symptoms, decreased libido, osteoporosis and fractures were more frequent with OFS plus exemestane). Thus, the combinations of OFS (with triptorelin) plus either tamoxifen or an AI are valid options for the adjuvant treatment of endocrine-responsive, early-stage breast cancer in women at sufficiently high risk of relapse to warrant receiving chemotherapy and who remain premenopausal thereafter. Individualized weighing of the potential benefits and adverse effects of treatment is required.

Oncoplastic reduction mammoplasty for breast cancer in women with macromastia: long term aesthetic, functional and satisfaction outcomes.

Aim of the studyDespite the increase in studies concerning oncoplastic reduction mammoplasty (ORM), data showing long-term aesthetic and patient satisfaction for ORM in patients with macromastia remain limited. Therefore, this study evaluated the long-term results of tumorectomy and concomitant bilateral ORM for early-stage breast cancer patients with macromastia in terms of cosmesis, patient satisfaction, and functional outcomes.Material and methodsRetrospective data of patients with macromastia undergoing ORM for breast cancer between 1996 and 2011 were examined and evaluated regarding the aesthetic results, patient satisfaction, and functional outcomes.ResultsThe median age of the 82 patients was 50 years. The median follow-up was 120 months (range: 28–212 months). The median breast volume was 1402 cm3, and the median weight of the excised breast material was 679 g. A good or excellent evaluation of the cosmetic outcome was as follows: self-evaluation: 84.1% at the early-stage, 80.3% at the later stage; panel evaluation: 75.4% at the late-stage. Median patient satisfaction rates were 9.1% for early-stage disease and 8.8% for late-stage disease. Reduced mobility and intertrigo improved by three-fold during the post-operative period.ConclusionsORM for early-stage breast cancer in women with macromastia results in good cosmesis in both the early-stage and long-term, and is quite acceptable for use in patients. Patients reacted favorably to the prospect of having their breast cancer and macromastia treated in a single session, and positive results continued over the long-term.

Elevated free IGF2 levels in localized, early-stage breast cancer in women

Epidemiological studies imply an association between circulating IGF1 and breast cancer, whereas the role of IGF2, which also acts on the IGF1 receptor, is less settled. This study investigates the association between IGF2 and breast cancer in patients with localized disease. The participants were women with well-characterized, early stage, localized breast cancer (n=43) and matched healthy women (n=38), from whom fasting serum levels of IGF-related peptides were measured. In patients, mean free IGF2 was increased (+57%, P<0.001), in spite of reduced total IGF2 levels (-12%, P=0.003) when compared with controls. Similar changes were seen in free IGF1 (+28%, P=0.004) and total IGF1 (-16% P=NS). Pro-IGF2 and IGF-binding protein 1 (IGFBP1) were unchanged. IGFBP2 was reduced by 22% in the patients (P=0.004). The patients showed reduced IGFBP3 protease activity and accordingly increased levels of intact IGFBP3, whereas total IGFBP3 was unchanged. Women with localized, early-stage breast cancer show elevated circulating free IGF1 and IGF2, reduced total IGF2 and alterations in IGFBPs. The changes observed despite minimal cancer disease suggest a role for the circulating IGF system in the progression of breast cancer in women.