Occurrence of breast-cancer-related lymphedema after reverse lymphatic mapping and selective axillary dissection versus standard surgical treatment of axilla: A two-arm randomized clinical trial.

BACKGROUND: The need for axillary dissection (AD) is declining, but it is still essential for many patients with nodal involvement who risk developing breast-cancer-related lymphedema (BCRL) with lifelong consequences. Previous nonrandomized studies found axillary reverse mapping and selective axillary dissection (ARM-SAD) a safe and feasible way to preserve the arm's lymphatic drainage. METHODS: The present two-arm prospective randomized clinical trial was held at a single comprehensive cancer center to ascertain whether ARM-SAD can reduce the risk of BCRL, compared with standard AD, in patients with node-positive breast cancer. Whatever the type of breast surgery or adjuvant treatments planned, 130 patients with nodal involvement met our inclusion criteria: 65 were randomized for AD and 65 for ARM-SAD. Twelve months after surgery, a physiatrist assessed patients for BCRL and calculated the excess volume of the operated arm. Lymphoscintigraphy was used to assess drainage impairment. Self-reports of any impairment were also recorded. RESULTS: The difference in the incidence of BCRL between the two groups was 21% (95% CI, 3-37; p = .03). A significantly lower rate of BCRL after ARM-SAD was confirmed by a multimodal analysis that included the physiatrist's findings, excess arm volume, and lymphoscintigraphic findings, but this was not matched by a significant difference in patients' self-reports. CONCLUSIONS: Our findings encourage a change of surgical approach when AD is still warranted. ARM-SAD may be an alternative to standard AD to reduce the treatment-related morbidity.

Hypofractionated irradiation in 794 elderly breast cancer patients: An observational study.

To assess the efficacy, and the acute and late toxicity of hypofractionated radiotherapy (Hypo-RT), and the impact of age and comorbidities on disease progression and death in elderly breast cancer (BC) patients. Women aged ≥65 years who received Hypo-RT (42.4 Gy in 16 fractions, plus a boost for high-risk patients) were considered for the present analysis. Competing risk analysis was used to estimate the 5-year cumulative incidence of BC progression and BC-related death, calculating the adjusted subhazard ratios (SHR) with 95% confidence intervals (95%CI) in relation to age, hypertension-augmented Charlson Comorbidity Index (hCCI), tumor characteristics, and chemotherapy. The sample included 794 patients with a median age of 74 years (range 65-91 years). At the baseline, 70% of these patients had at least one comorbidity. With a median follow-up of 48.3 months, the 5-year cumulative incidence of BC progression and BC-related death was 6.7% (95%CI 4.8%-9.2%) and 2.3% (95%CI 1.2%-3.9%), respectively. Old age (≥80 years) and a high burden of comorbidity (hCCI ≥ 2) were independently associated with BC progression. Hypo-RT is safe in elderly BC patients, but age and comorbidities influence BC progression. Further studies are warranted.

Skin-Reducing Mastectomy and Direct-to-Implant Breast Reconstruction With Submuscular-Dermal-Mesh Pocket.

BACKGROUND: Despite skin-sparing mastectomy techniques have significantly improved reconstructive options and aesthetic outcomes, patients with large and ptotic breasts remain a challenging group to treat satisfactorily. The Wise-pattern skin-reducing mastectomy (SRM) has been designed for this kind of patients but is not without morbidity. To improve safety, the authors reviewed their experience with a modified SRM and immediate 1-stage implant-based breast reconstruction, using a synthetic absorbable mesh combined with a dermal flap. METHODS: A retrospective review was undertaken to identify women with medium to large ptotic breast and medium minimally ptotic breast who had undergone SRM and direct-to-implant breast reconstruction using definitive anatomical gel implant, de-epithelialized dermal flap, and absorbable synthetic mesh, between October 2014 and December 2016. Patient demographics were queried, and complication rates, aesthetic outcomes, and patients satisfaction were assessed. RESULTS: Sixty-two procedures of SRM were performed in 56 patients. Forty-five women received contralateral symmetrization. Twenty-one overall complications occurred in 16 patients. Statistical correlation between risk factors and complications onset was assessed. Body mass index resulted the most substantial risk factor (P = 0.0028) for developing complications, whereas preoperative chemotherapy (P = 0.0050) and comorbidities (P = 0.0117) played a decent role. Smoking attitude (P = 0.1122), age (P = 0.9990), and implant weight (P = 0.1583) did not result as significant risk factors. The reconstructive outcomes were good to excellent in 92.8%, with patient satisfaction ranking very to highly satisfied in 84%. CONCLUSIONS: The authors' series suggests that SRM with direct-to-implant breast reconstruction can be easily performed when an appropriate SRM pattern is designed, providing complete implant coverage with submuscular-dermal-mesh pocket.

Assessing the Risk of Occult Cancer and 30-day Morbidity in Women Undergoing Risk-reducing Surgery: A Prospective Experience.

STUDY OBJECTIVE: To investigate the incidence and predictive factors of 30-day surgery-related morbidity and occult precancerous and cancerous conditions for women undergoing risk-reducing surgery. DESIGN: A prospective study (Canadian Task Force classification II-1). SETTING: A gynecologic oncology referral center. PATIENTS: Breast-related cancer antigen (BRCA) mutation carriers and BRCAX patients (those with a significant family history of breast and ovarian cancer). INTERVENTIONS: Minimally invasive risk-reduction surgery. MEASUREMENTS AND MAIN RESULTS: Overall, 85 women underwent risk-reducing surgery: 30 (35%) and 55 (65%) had hysterectomy plus bilateral salpingo-oophorectomy (BSO) and BSO alone, respectively. Overall, in 6 (7%) patients, the final pathology revealed unexpected cancer: 3 early-stage ovarian/fallopian tube cancers, 2 advanced-stage ovarian cancers (stage IIIA and IIIB), and 1 serous endometrial carcinoma. Additionally, 3 (3.6%) patients had incidental finding of serous tubal intraepithelial carcinoma. Four (4.7%) postoperative complications within 30 days from surgery were registered, including fever (n = 3) and postoperative ileus (n = 1); no severe (grade 3 or more) complications were observed. All complications were managed conservatively. The presence of occult cancer was the only factor predicting the development of postoperative complications (p = .02). CONCLUSION: Minimally invasive risk-reducing surgery is a safe and effective strategy to manage BRCA mutation carriers. Patients should benefit from an appropriate counseling about the high prevalence of undiagnosed cancers observed at the time of surgery.

Axillary lymph node dissection versus no dissection in patients with T1N0 breast cancer: a randomized clinical trial (INT09/98).

BACKGROUND: Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS: From June 1998 to June 2003, 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or without (QU) axillary lymph node dissection; a total of 517 patients finally were evaluated. All patients received radiotherapy to the residual breast only. Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status, estrogen receptor status, and tumor grade. Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status, tumor grade, and human epidermal growth factor receptor 2 and laminin receptor status. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints. RESULTS: After a median follow-up of >10 years, the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95% confidence interval, 0.59-2.00; P = .783) and was 1.04 (95% confidence interval, 0.56-1.94; P = .898) for DFS. Of the 245 patients in the QU treatment arm, 22 (9.0%) experienced axillary lymph node recurrence. The median time to axillary lymph node recurrence from breast surgery was 30.0 months (interquartile range, 24.2 months-73.4 months). CONCLUSIONS: Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial. The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment.

Clinical recommendations for treatment of localized angiosarcoma: A consensus paper by the Italian Sarcoma Group.

Angiosarcoma (AS) represents a rare and aggressive vascular sarcoma, posing distinct challenges in clinical management compared to other sarcomas. While the current European Society of Medical Oncology (ESMO) clinical practice guidelines for sarcoma treatment are applicable to AS, its unique aggressiveness and diverse tumor presentations necessitate dedicated and detailed clinical recommendations, which are currently lacking. Notably, considerations regarding surgical extent, radiation therapy (RT), and neoadjuvant/adjuvant chemotherapy vary significantly in localized disease, depending on each different site of onset. Indeed, AS are one of the sarcoma types most sensitive to cytotoxic chemotherapy. Despite this, uncertainties persist regarding optimal management across different clinical presentations, highlighting the need for further investigation through clinical trials. The Italian Sarcoma Group (ISG) organized a consensus meeting on April 1st, 2023, in Castel San Pietro, Italy, bringing together Italian sarcoma experts from several disciplines and patient representatives from "Sofia nel Cuore Onlus" and the ISG patient advocacy working group. The objective was to develop specific clinical recommendations for managing localized AS within the existing framework of sarcoma clinical practice guidelines, accounting for potential practice variations among ISG institutions. The aim was to try to standardize and harmonize clinical practices, or at least highlight the open questions in the local management of the disease, to define the best evidence-based practice for the optimal approach of localized AS and generate the recommendations presented herein.

Magnetic Localization of Breast Lesions: A Large-Scale European Evaluation in a National Cancer Institute.

INTRODUCTION: For decades the standard for preoperative breast lesions' localization has been wire localization. In recent years the options for nonwired localization have significantly expanded and include radioactive seeds, radar reflectors, radiofrequency identification tags and magnetic seeds. The aim of our study is to evaluate on a large scale the performance of preoperative magnetic seed localization of nonpalpable breast lesions. MATERIAL AND METHODS: We prospectively collected data on all patients undergoing image-guided magnetic seed localization from September 2019 to December 2022. We analyzed imaging findings, histological results, and type of surgery. The primary outcome was the successful localization rate. Secondary outcomes were the successful placement rate, the ease of percutaneous positioning, the procedural complications, and the reintervention rate. RESULTS: A total of 1123 magnetic seeds were placed in 1084 patients by 4 radiologists under ultrasound (1053) or stereotactic (70) guidance. All seeds were detectable transcutaneously in all breasts sizes and at all depths by 7 surgeons with a success rate of 100%. A total of 97.5% seeds were correctly placed into the target lesions (only 2.5% were dislocated). All radiologists have shown good compliance during the procedure, and there were no complications or safety issues. The reoperation rate was 5.1%. CONCLUSIONS: Image-guided localization with magnetic seeds is an easy, safe, reliable, and effective method for localizing nonpalpable breast lesions. Both radiologists and surgeons agreed that the technology was intuitive to use and that it can be widely applied in preoperative localization in breast units.

Treating secondary malignant neoplasms: A burden of childhood cancer survivors.

Each year approximately 35,000 children and adolescents are diagnosed with cancer in Europe. Five-year survival rates have improved and now reach 80% in most European countries, thanks to a combination of chemotherapy, radiotherapy, and surgery. To date, there are more than 44,000 Italians still living several years after being diagnosed with cancer in developmental age. The risk of premature morbidity and mortality for cancer survivors is well known and documented. Approximately 60% of survivors of cancer in childhood and adolescence have at least one chronic health condition in later life, and more than one in four develop severe or life-threatening disorders. Among the various long-term iatrogenic sequelae of cancer treatments, the most worrisome are second malignant neoplasms. We reported on our mono-institutional experiences of screening and treating secondary breast cancer, secondary thyroid cancer and secondary osteosarcoma. Recommendations on the surveillance needed for cancer survivors because of the risk of late effects of their disease or its treatment suggest that discussing the potential problems early on can be crucial to a patient's future health. These considerations and our consolidated experience strengthen our conviction that survivors of cancer in childhood and adolescence who develop second malignant neoplasms should be treated at highly-specialized centers. Multidisciplinary care requires close communications and high levels of up-to-date professional expertise. This challenging area of health care is also changing rapidly because cancer survivorship is a work in progress, but we cannot wait for definitive conclusions on many aspects because this will take decades, especially for pediatric patients.

Oncological safety of selective axillary dissection after axillary reverse mapping in node-positive breast cancer.

INTRODUCTION: Although the need for axillary lymph node dissection (AD) is decreasing in breast cancer patients, it remains necessary in some cases. Axillary reverse mapping (ARM) enables the detection of upper extremity lymphatic drainage that may be spared during selective axillary dissection (SAD) so as to reduce the risk of lymphedema. The ability of the ARM-SAD procedure to reduce the incidence of lymphedema is being tested in an ongoing randomized trial. Crossover between arm drainage and breast drainage is well documented in the axilla, however, and whether the procedure is oncologically safe remains controversial. We aim to assess the axillary failure rate when a few nodes draining the upper arm are being spared by the ARM-SAD. METHODS: We report oncological outcomes, and axillary failure in particular, in the first 100 consecutive axillary node-positive patients treated with ARM-SAD as part of a pilot study and a randomized trial. RESULTS: A median of 18 (IQR 14-22) axillary nodes were excised per patient. During the follow-up (median 51 months, IQR 34-91), 11 patients experienced a treatment failure, but only one - treated with neoadjuvant chemotherapy - developed overt axillary disease as a first (and isolated) event. The crude rate of axillary failure was 1.36% (95% CI: 0.19-9.63) with an estimated 5-year crude cumulative incidence of 1.85% (95% CI: 0-5.47%). CONCLUSIONS: The axillary failure rate was low in our patients and did not exceed rates reported in the literature after standard AD, thus indicating that the ARM-SAD procedure is oncologically safe.

A combination of extracellular matrix- and interferon-associated signatures identifies high-grade breast cancers with poor prognosis.

Breast cancer (BC) is a heterogeneous disease in which the tumor microenvironment (TME) seems to impact the clinical outcome. Here, we investigated whether a combination of gene expression signatures relating to both the structural and immune TME aspects can help predict prognosis in women with high-grade BC (HGBC). Thus, we focused on a combined molecular biomarker variable that involved extracellular matrix (ECM)-associated gene expression (ECM3 signature) and interferon (IFN)-associated metagene (IFN metagene) expression. In 97 chemo-naive HGBCs from the METABRIC dataset, the dichotomous ECM3/IFN (dECIF) variable identified a group of high-risk patients (ECM3+ /IFN- vs other; hazard ratio = 3.2, 95% confidence interval: 1.5-6.7). Notably, ECM3+ /IFN- tumors showed low tumor-infiltrating lymphocytes, high levels of CD33-positive cells, absence of PD-1 expression, or low expression of PD-L1, as suggested by immune profiles and immune-histochemical analysis on an independent cohort of 131 HGBCs. To make our results transferable to clinical use, we refined the dECIF biomarker using reduced ECM3 and IFN signatures; notably, the prognostic value of this reduced dECIF was comparable to that of the original dECIF. After validation in a new BC cohort, reduced dECIF was translated into a robust qPCR classifier for real-world clinical use.

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.

Recurrence and mortality according to estrogen receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast.

BACKGROUND: The study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. METHODS: Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. RESULTS: DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. CONCLUSION: DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues.

Angiosarcoma of the breast and vascular endothelial growth factor receptor.

BACKGROUND: Breast angiosarcoma is rare and often associated with previous breast cancer treatment. The present study aimed to define long-term outcomes in relation to common prognostic factors. The expression of vascular endothelial growth factor receptor was also evaluated, as it may be a potential target for anti-angiogenic therapy. PATIENTS AND METHODS: We retrospectively assessed outcomes in relation to age, association with previous breast-conserving treatment for breast cancer, tumor size, and grade in 19 patients without metastases at diagnosis. Vascular endothelial growth factor receptor was also assessed. RESULTS: Median follow-up was 33 months (range, 1-121). There were 6 local recurrences and 6 deaths for disease progression. Five-year disease-free survival and overall survival were 53% (95% CI, 20-86%) and 49% (95% CI, 14-84%), respectively. No factor significantly affected survival. Vascular endothelial growth factor receptor was positive in 50% of cases and was more frequent in better differentiated cancer. CONCLUSIONS: The association of vascular endothelial growth factor receptor with G1/G2 tumors requires further investigations. Our findings suggest that anti-angiogenic treatment in vascular endothelial growth factor receptor-positive cases be considered as a novel therapeutic modality in this rare and aggressive disease. Although information is still incomplete, we propose a multimodal therapeutic approach including surgery, radiotherapy and chemotherapy.

High consistency between characteristics of primary intraductal breast cancer and subtype of subsequent ipsilateral invasive cancer.

BACKGROUND: Ductal carcinoma in situ (DCIS) is considered a morphologic precursor of invasive cancer and is often treated with adjuvant whole-breast irradiation and endocrine therapy, as if it were an invasive cancer. Our aim was to provide further support for treatment de-escalation or enrollment of such patients in active surveillance trials. METHODS: We retrospectively analyzed data on patients with conservatively treated primary DCIS subsequently diagnosed with ipsilateral invasive breast cancer (IBC) at 2 comprehensive breast cancer centers. From their merged databases, we identified 50 cases with full details on tumor grade, hormone receptor expression, and HER2 amplification, for both the primary DCIS and the corresponding IBC, and we assessed the similarities and differences between the two. RESULTS: Distributions of hormone receptors were similar in primary DCIS and IBC, while high-grade and HER2-positive status was less common in IBC than in primary DCIS. The positivity for estrogen receptors (ER) and well-differentiated or moderately differentiated morphology in the primary DCIS persisted in 90% of the matching IBC. Changes in progesterone receptor expression were slightly more common than those in ER expression. Overall consistency for the luminal-like receptors subtype was found in 90% of cases. CONCLUSION: The high consistency between the features of primary DCIS and those of subsequent IBC (in the rare but not negligible cases of local failure) should be borne in mind when considering the therapeutic options. Treatment de-escalation and accrual of patients for active surveillance trials could be appropriate for luminal-like precursors.

Interobserver variability (between radiation oncologist and radiation therapist) in tumor bed contouring after breast-conserving surgery.

PURPOSE: To examine interobserver variability between the radiation oncologist (RTO) and the radiation therapist (RTT) in delineating the tumor bed (TB) in early breast cancer (BC). METHODS: We retrospectively analyzed patients who received a radiotherapy boost to the TB. In a first group, the clinical target volume (CTV) for the boost was the surgical bed, defined by using surgical clips. In a second group, the CTV was defined by identifying a seroma cavity or a metallic find on the scar. These contours were compared in terms of volume, number of slices, and Dice similarity coefficient (DSC). RESULTS: Forty patients were assessed: 20 had surgical clips (group 1) while the other 20 had none (group 2). There was no difference in the number of slices contoured by the 2 operators for group 1, but a statistically significant difference emerged in the volumes: the RTT identified a TB that was a mean 45% smaller than the one identified by the RTO. Random differences were found between the 2 operators for group 2. The TBs delineated for this group were significantly larger (P<0.05) than those identified by the RTT for group 1. The mean Dice value between the RTO's and the RTT's TBs was 0.69±0.07 (range 0.53-0.81) for group 1 and 0.37±0.18 (range 0-0.58) for group 2 (P<0.05). CONCLUSIONS: This study showed that the use of clips coincided with less interoperator variability. With appropriate training, the RTT may play an important part in the multidisciplinary radiotherapy team.

Surgical delay may extend the indications for nipple-sparing mastectomy: A multicentric study.

INTRODUCTION: Nipple-sparing mastectomy (NSM) is considered an oncologically sound procedure but necrosis of the nipple-areola complex (NAC) or skin flaps is a concern, particularly in the presence of risk factors. To increase the indications for NSM and decrease such complications, different procedures of "surgical delay" (SD) have been described. MATERIALS AND METHODS: A retrospective analysis of patients who underwent SD for NSM at four Italian Breast Centers from 2014 to 2017 was performed. SD generally consisted of a periareolar or "hemi-batwing" incision, dissecting the skin and the NAC from the underlying breast tissue. NSM was scheduled after 2-3 weeks. RESULTS: Eighty-eight procedures were analyzed. Mild complications of SD were registered in 7.9% of cases. NSM was performed in 85 cases, whereas in three cases (3.4%) a "skin-sparing" mastectomy was necessary due to positivity of the retroareolar biopsy for cancer at SD. A direct-to- implant (DTI) reconstruction was performed in 42 cases (49.4%), while in 43 (50.6%) a tissue-expander (TE) was inserted. After NSM, eight complications (9.4%) were recorded: one total necrosis (1.2%), one partial necrosis (1.2%) and four minimal ischemia (4.7%) of NAC, one skin flap necrosis (1.2%), one haematoma (1.2%). In only two cases (2.3%) prosthesis removal was needed. Aesthetic outcome was evaluated excellent or good in 92.9% of cases. At a median follow-up of 24 months no local recurrences were seen. CONCLUSION: This is the largest series of SD with NSM presented so far in the literature. In our experience, SD extends indications for NSM in high-risk women.

Psychological assessment of women on an early breast screening program after radiotherapy to the chest wall for childhood cancer.

AIMS AND BACKGROUND: This study investigates the psychological status in a population of female patients who received chest irradiation for a childhood cancer and were screened for second primary breast cancer. METHODS: Sixty-eight consecutive such young women were included. Compilation of the Crown-Crisp Index questionnaire was requested and 49/68 patients accepted to fill it in; 14 women in the sample had children (28%). RESULTS: Twenty-seven of 49 patients achieved a normal score, whereas in 22 the score was slightly above the normal range in at least one scale. Pathological scores were more frequent among the women without children. CONCLUSION: Quality of life in this series of long-term survivors does not seem to be severely affected by previous treatment for cancer nor by the concern for the onset of a second primary malignancy.

Discontinuation of hormone therapy for elderly breast cancer patients after hypofractionated whole-breast radiotherapy.

The purpose of the study was to examine adherence to hormone therapy (HT) in elderly breast cancer patients (≥ 65 years old) treated with hypofractionated radiotherapy. We analyzed data on 550 ER-positive breast cancer patients given hypofractionated whole-breast radiotherapy from June 2009 to September 2016. Baseline comorbidities considered in the hypertension-augmented Charlson Comorbidity Index (hCCI) were retrospectively retrieved. Total hCCI scores were classified as no comorbidity (hCCI = 0), low burden of comorbidity (hCCI = 1), and high burden of comorbidity (hCCI ≥ 2). Competing risk analysis was used to estimate the 5-year cumulative incidence of HT discontinuation. Fine and Gray models were used to estimate the adjusted subhazard ratio (SHR) of HT discontinuation by hCCI score. HT was initially prescribed for 85.6% of patients and almost all of them (468/471) took it for at least one month. It was subsequently discontinued by 45 patients (9.6%), for an overall 5-year cumulative incidence of 11.7%. The 5-year cumulative incidence of HT discontinuation rose from 3.9% in the youngest age group (65-69 years) to 23.3% in the oldest (≥ 80 years) (p = 0.005). Baseline comorbidity had some effect on the likelihood of discontinuing HT, but only among patients with a low burden of comorbidity (hCCI = 1, SHR 2.00, 95%CI 0.95-4.20). Adherence to HT was better in our sample than in the literature, probably because patients were selected and motivated to continue HT. This confirms the importance of communication with patients to improve adherence to HT. We confirmed the association between HT discontinuation and older age, while comorbidity had a limited influence.

Dynamics of the hazard for distant metastases after ipsilateral breast tumor recurrence according to estrogen receptor status: An analysis of 2851 patients.

BACKGROUND: Breast cancer (BC) patients with ipsilateral breast tumor recurrence (IBTR) are at high risk of developing distant metastases (DM). We aimed to evaluate the risk pattern of developing DM, with respect to the occurrence of IBTR, in a large series of patients homogeneously treated by conservative surgery (QUART) with a considerably long follow-up. METHODS: Piecewise exponential model was used to investigate DM dynamics conditioning on known prognostic factors and IBTR occurrence as time dependent covariate. The model was extended to account for the timescale induced by IBTR, namely the time elapsed since IBTR to the endpoint. RESULTS: Among 2851 BCE patients receiving QUART, 209 were assessable for IBTR. After a median follow-up of 129 months, 588 patients presented DM (CCI = 27.3%) as first event and 92 (CCI = 48.8%) following IBTR. Primary tumor size and nodal status confirmed their prognostic value. The hazard for DM was early and high in Estrogen Receptor (ER) negative BC patients; while it was initially low but increases during follow-up in ER positive cases. Patients experiencing IBTR showed DM dynamic similar to that following primary tumor, with a sudden increased risk within 24 months from surgery, regardless the time elapsed since QUART. CONCLUSION: BC patients experiencing IBTR showed a sudden and sustained risk of DM following surgery. Our findings are consistent with the hypothesis that IBTR occurrence might act as a "time resector" for risk of DM, and provide a rationale for proper surveillance guidelines and systemic therapy for optimizing BC recurrence and appropriate choice of treatment.