Alternative dosing regimen of exemestane in a randomized presurgical trial: the role of obesity in biomarker modulation.

In a 3-arm presurgical trial, four-six weeks exemestane 25 mg three times/week (TIW) was non-inferior to 25 mg/day (QD) in suppressing circulating estradiol in postmenopausal women with ER-positive breast cancer. Since obesity may decrease exemestane efficacy, we analyzed changes in sex steroids, adipokines, Ki-67, and drug levels in relation to obesity. Postmenopausal women with early-stage ER-positive breast cancer were randomized to either exemestane 25 mg QD (n = 57), 25 mg TIW (n = 57), or 25 mg/week (QW, n = 62) for 4-6 weeks before breast surgery. Serum and tissue pre- and post-treatment biomarkers were stratified by body mass index (BMI)< or ≥30 kg/m2. Post-treatment median exemestane and 17-OH exemestane levels were 5-6 times higher in the QD arm compared to the TIW arm. For obese women, TIW maintained comparable reductions to QD in systemic estradiol levels, although the reduction in estrone was less with the TIW regimen. There was less suppression of SHBG with the TIW versus the QD dose schedule in obese women which should result in less systemic bioavailable estrogens. Metabolically, the effect of the TIW regimen was similar to the QD regimen for obese women in terms of leptin suppression and increase in the adiponectin-leptin ratio. Reduction in tissue Ki-67 was less for obese women on the TIW regimen than QD, although changes were similar for non-obese women. Our findings suggest that TIW exemestane should be explored further for primary cancer prevention in both normal weight and obese cohorts.

The Role of Sentinel Lymph Node Biopsy in Breast Cancer Patients Who Become Clinically Node-Negative Following Neo-Adjuvant Chemotherapy: A Literature Review.

BACKGROUND: In clinically node-positive (cN+) breast cancer (BC) patients who become clinically node-negative (cN0) following neoadjuvant chemotherapy (NACT), sentinel lymph node biopsy (SLNB) after lymphatic mapping with lymphoscintigraphy is not widely accepted; therefore, it has become a topic of international debate. OBJECTIVE: Our literature review aims to evaluate the current use of this surgical practice in a clinical setting and focuses on several studies published in the last six years which have contributed to the assessment of the feasibility and accuracy of this practice, highlighting its importance and oncological safety. We have considered the advantages and disadvantages of this technique compared to other suggested methods and strategies. We also evaluated the role of local irradiation therapy after SLNB and state-of-the-art SLN mapping in patients subjected to NACT. METHODS: A comprehensive search of PubMed and Cochrane was conducted. All studies published in English from 2018 to August 2023 were evaluated. RESULTS: Breast units are moving towards a de-escalation of axillary surgery, even in the NACT setting. The effects of these procedures on local irradiation are not very clear. Several studies have evaluated the oncological outcome of SLNB procedures. However, none of the alternative techniques proposed to lower the false negative rate (FNR) of SLNB are significant in terms of prognosis. CONCLUSIONS: Based on these results, we can state that lymphatic mapping with SLNB in cN+ BC patients who become clinically node-negative (ycN0) following NACT is a safe procedure, with a good prognosis and low axillary failure rates.

Efficacy of Alternative Dose Regimens of Exemestane in Postmenopausal Women With Stage 0 to II Estrogen Receptor-Positive Breast Cancer: A Randomized Clinical Trial.

Importance: Successful therapeutic cancer prevention requires definition of the minimal effective dose. Aromatase inhibitors decrease breast cancer incidence in high-risk women, but use in prevention and compliance in adjuvant settings are hampered by adverse events. Objective: To compare the noninferiority percentage change of estradiol in postmenopausal women with estrogen receptor-positive breast cancer given exemestane, 25 mg, 3 times weekly or once weekly vs a standard daily dose with a noninferiority margin of -6%. Design, Setting, and Participants: This multicenter, presurgical, double-blind phase 2b randomized clinical trial evaluated 2 alternative dosing schedules of exemestane. Postmenopausal women with estrogen receptor-positive breast cancer who were candidates for breast surgery were screened from February 1, 2017, to August 31, 2019. Blood samples were collected at baseline and final visit; tissue biomarker changes were assessed from diagnostic biopsy and surgical specimen. Biomarkers were measured in different laboratories between April 2020 and December 2021. Interventions: Exemestane, 25 mg, once daily, 3 times weekly, or once weekly for 4 to 6 weeks before surgery. Main Outcomes and Measures: Serum estradiol concentrations were measured by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry detection. Toxic effects were evaluated using the National Cancer Institute terminology criteria, and Ki-67 was assessed by immunohistochemistry. Results: A total of 180 women were randomized into 1 of the 3 arms; median (IQR) age was 66 (60-71) years, 63 (60-69) years, and 65 (61-70) years in the once-daily, 3-times-weekly, and once-weekly arms, respectively. In the intention-to-treat population (n = 171), the least square mean percentage change of serum estradiol was -89%, -85%, and -60% for exemestane once daily (n = 55), 3 times weekly (n = 56), and once weekly (n = 60), respectively. The difference in estradiol percentage change between the once-daily and 3-times-weekly arms was -3.6% (P for noninferiority = .37), whereas in compliant participants (n = 153), it was 2.0% (97.5% lower confidence limit, -5.6%; P for noninferiority = .02). Among secondary end points, Ki-67 and progesterone receptor were reduced in all arms, with median absolute percentage changes of -7.5%, -5.0%, and -4.0% for Ki-67 in the once-daily, 3-times-weekly, and once-weekly arms, respectively (once daily vs 3 times weekly, P = .31; once daily vs once weekly, P = .06), and -17.0%, -9.0%, and -7.0% for progesterone receptor, respectively. Sex hormone-binding globulin and high-density lipoprotein cholesterol had a better profile among participants in the 3-times-weekly arm compared with once-daily arm. Adverse events were similar in all arms. Conclusions and Relevance: In this randomized clinical trial, exemestane, 25 mg, given 3 times weekly in compliant patients was noninferior to the once-daily dosage in decreasing serum estradiol. This new schedule should be further studied in prevention studies and in women who do not tolerate the daily dose in the adjuvant setting. Trial Registration: ClinicalTrials.gov Identifier: NCT02598557; EudraCT: 2015-005063-16.

Approaches to Fertility Preservation for Young Women With Breast Cancer.

In patients with early breast cancer, the combination of different systemic treatment strategies, including chemotherapy, endocrine therapy, targeted therapy, and more recently also immunotherapy has demonstrated to significantly improve their survival outcomes. However, this gain is often obtained at the cost of higher toxicity calling for the need of increased attention toward survivorship-related issues, including fertility preservation in young women. According to available guidelines, health care providers should offer oncofertility counseling to all patients with cancer diagnosed at reproductive age. Counselling should focus on the risk of gonadotoxicity of anticancer treatments and on the access to fertility preservation techniques. However, several surveys have demonstrated suboptimal implementation of these recommendations. This review aims at summarizing the available evidence on oncofertility to guide health care providers involved in the management of young women with breast cancer. Available and effective options for fertility preservation include oocyte/embryo cryopreservation or ovarian tissue cryopreservation. Patient, disease, and treatment characteristics should be carefully considered when offering these strategies. Ovarian function preservation with gonadotrophin-releasing hormone agonists during chemotherapy should be discussed and offered to every premenopausal woman concerned about developing premature ovarian insufficiency and independently of her wish to preserve fertility. Current available data confirm that pregnancy occurring after proper treatment for breast cancer is safe, both in terms of long-term clinical outcomes and for the babies. Fertility preservation and pregnancy desire should be pivotal components of the multimodal management of breast cancer in young women, and require a multidisciplinary approach based on close collaborations between oncologists and fertility specialists.

Choosing the appropriate pharmacotherapy for breast cancer during pregnancy: what needs to be considered?

INTRODUCTION: Breast cancer is the most commonly diagnosed malignancy during pregnancy. Breast cancer during pregnancy is a challenging clinical condition requiring proper and timely multidisciplinary management. AREAS COVERED: This review focuses on the management of breast cancer during pregnancy with a focus about the current state-of-the-art on the feasibility and safety of pharmacotherapy approaches in this setting. EXPERT OPINION: Multidisciplinary care is key for a proper diagnostic-therapeutic management of breast cancer during pregnancy. Engaging patients and their caregivers in the decision-making process is essential and psychological support should be provided. The treatment of patients with breast cancer during pregnancy should follow the same recommendations as those for breast cancer in young women outside pregnancy but taking into account the gestational age at the time of treatment.Anthracycline-, cyclophosphamide-, and taxane-based regimens can be safely administered during the second and third trimesters with standard protocols, preferring weekly regimens whenever possible. Endocrine therapy, immune checkpoint inhibitors, and targeted agents are contraindicated throughout pregnancy, also due to the very limited data available to guide their administration in this setting. During treatment, careful fetal growth monitoring is mandatory, and even after delivery proper health monitoring for the children exposed in utero to chemotherapy should be continued.

Perforator flaps for vulvar reconstruction: basic principles.

BACKGROUND AND AIM: In vulvar cancer, the standard treatment is radical local excision, with immediate reconstruction. Reconstruction aims to restore anatomy and function of the external female genitalia, facilitating preservation of normal body image, sexual function, and micturition and defecation functions. METHODS: The purpose of this paper is to describe the principles of perforator flaps for vulvar reconstruction. RESULTS: Basic concepts, indications and operative technique are discussed and detailed. CONCLUSIONS: In vulvar reconstruction, the use of perforator flaps is a superior surgical technique when compared to the use of conventional flaps.

Update on Pregnancy Following Breast Cancer Diagnosis and Treatment.

ABSTRACT: Survivorship has become a crucial component in breast cancer care. For women who have not completed their family planning, conceiving at the end of anticancer treatments should not be discouraged but might be challenging. Oncofertility counseling should be offered at the time of diagnosis to all patients, in order to inform them about the potential treatment-induced gonadotoxicity as well as the available strategies for fertility preservation, thus allowing to increase the chances of a future pregnancy. This article reports an updated overview on the current state of the art on pregnancy in women with prior breast cancer diagnosis and treatment, with a main focus on the issues faced by patients with history of hormone receptor-positive disease and BRCA carriers.

"The use of Autologous Flaps in Breast Reshaping After Massive Weight Loss: A Systematic Review".

BACKGROUND: Massive weight loss (MWL) has a positive impact on the comorbidities associated with obesity but leaves patients with ongoing body issues due to skin excess. Almost all patients present some degree of breast ptosis and breast volume deficiency, which can be addressed with different techniques including autologous flaps. MATERIAL AND METHODS: A literature search was conducted by using PubMed, Google Scholar, and Cochrane databases. Patient's characteristics, type of bariatric surgery, amount of weight loss, flap size and design, simultaneous breast and extra-breast procedures were analyzed. Aesthetic and patient-reported outcomes, postoperative complications, revision rate, and donor site morbidity were also registered. RESULTS: Twelve articles fulfilled inclusion criteria, and 79 patients were included, for a total of 157 flaps. Different flap designs and flap combinations were described; those originating from lateral chest wall area were the most commonly used. Simultaneous breast procedures were reported in 72 patients. Simultaneous extra-breast body contouring (BC) procedure was performed in 40 cases. The overall complication rate was 9.55% and a total of ten revisionary procedures were performed. Satisfaction of the patients was globally quite high. CONCLUSIONS: Advantages of the use of autologous tissue in breast reshaping after MWL is the avoidance of implant-related complications and the simultaneous improvement of the silhouette. The complication rate resulted in acceptable, aesthetic, and patient-reported outcomes resulted to be encouraging, even if there was a lack of standardization in the evaluation. A comparative randomized study to confront the use of autologous flaps combined with mastopexy versus the use of implants combined with mastopexy can be useful to confirm the promising results. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

HER2-Low Breast Cancer: Where Are We?

Background: Breast cancer is traditionally classified into three clinical subtypes based on hormone receptor and HER2 status (i.e., luminal-like, HER2-positive, and triple negative). Each subtype has distinct clinical-pathological and molecular characteristics and requires tailored treatments. Recent research efforts have been focusing on a new classification, identifying the so-called "HER2-low" category, including tumors characterized by a low level of HER2 expression (immunohistochemistry score 1+ or 2+ without in situ hybridization amplification). Emerging evidence shows that patients with HER2-low tumors can derive benefit from selected anti-HER2 therapies. This represents a major advancement in the field of breast oncology, where a broader proportion of patients with breast cancer can ultimately benefit from new effective targeted treatment strategies. Summary: The antibody-drug conjugate trastuzumab deruxtecan has proven impressive efficacy in patients with HER2-low breast cancer, and several other drugs are currently under investigation in this subset of patients. Additional investigation is needed to address open issues that exist in this field, including appropriate pathological assessment of HER2-low status, clarification of its prognostic implications, and global access to newly approved drugs. Key Message: Our review aims to summarize the available evidence regarding HER2-low breast cancer, illustrating the current challenges that are being addressed and the future perspectives in this exciting new field.

Immunotherapy in Adolescents and Young Adults: What Remains in Cancer Survivors?

Immunotherapy has changed the landscape of treatments for advanced disease in multiple neoplasms. More and more patients are long survivors from a metastatic disease. Most recently, the extension of indications and evidence of efficacy in early disease settings, such as the adjuvant and neoadjuvant setting in breast cancer, lung cancer, glioma, and gastric cancer, places more attention on what happens to patients who survive cancer. In particular, we evaluated what happens in young patients, a population in whom some immune-related effects are still poorly described. Immunotherapy is already a reality in early disease settings and the scientific community is lagging in describing what to expect in adolescent and young adult (AYA) patients. For instance, the impact of these therapies on female and male fertility is not clear, similarly to the interaction that may occur between these drugs and pregnancy. This review aims to highlight these little-known topics that are difficult to evaluate in ad hoc studies.

How to Protect Ovarian Function before and during Chemotherapy?

A significant number of women receive a cancer diagnosis before their age of natural menopause. Among these patients, the most frequent neoplasms are breast cancer, gynecological, and hematological malignancies. Premature ovarian insufficiency and infertility are among the most feared short- to long-term consequences of anticancer treatments in premenopausal patients. Both patient- and treatment-related characteristics are key factors in influencing the risk of gonadotoxicity with the use of chemotherapy. The cryopreservation of oocytes/embryos is a standard strategy for fertility preservations offered to young women interested in future family planning, but it does not allow gonadal function protection during chemotherapy. Ovarian suppression with gonadotropin-releasing hormone agonist (GnRHa) during chemotherapy is now recommended as an option to reduce the risk of gonadotoxicity in order to avoid the negative consequences of premature ovarian insufficiency in premenopausal women receiving cytotoxic therapy, including those not interested in fertility preservation. This review summarizes the risk of treatment-induced gonadotoxicity in premenopausal patients and the evidence available on the protective role of administering GnRHa during chemotherapy to preserve ovarian function.

Alternative dosing of exemestane in postmenopausal women with ER-positive breast cancer. Design and methods of a randomized presurgical trial.

INTRODUCTION: Aromatase inhibitors are effective in lowering breast cancer incidence among postmenopausal women, but adverse events represent a barrier to their acceptability and adherence as a preventive treatment. This study aims to assess whether lowering exemestane schedule may retain biological activity while improving tolerability in breast cancer patients. METHODS/DESIGN: We are conducting a, pre-surgical, non-inferiority phase IIb study in postmenopausal women with newly diagnosed estrogen receptor-positive breast cancer. Participants are randomized to receive either exemestane 25 mg/day or 25 mg/three times-week or once a week for 4 to 6 weeks prior to surgery. The primary endpoint is the percentage change of serum estradiol concentration between baseline and surgery comparing the three arms. Sample size of 180 women was calculated assuming a 6% non-inferiority of the percent change of estradiol in the lower dose arms compared with the 80% decrease predicted in the full dose arm, with 80% power and using a one-sided 5% significance level and a two-sample t-test. Main secondary outcomes are: safety; change in Ki-67 in cancer and adjacent pre-cancer tissue, circulating sex hormones, adipokines, lipid profile, insulin and glucose changes, in correlation with drug and metabolites concentrations. RESULTS AND DISCUSSION: The present paper is focused on methodology and operational aspects of the study. A total of 180 participants have ben enrolled. The trial is still blinded, and the analyses are ongoing. Despite the short term duration, results may have relevant implications for clinical management of women at increased risk of developing a ER positive breast cancer.

Correlation between outcome and extent of residual disease in the sentinel node after neoadjuvant chemotherapy in clinically fine-needle proven node-positive breast cancer patients.

BACKGROUND: Whether the extent of residual disease in the sentinel lymph node (SLN) after neoadjuvant chemotherapy (NAC) influences the prognosis in clinically node-positive breast cancer (BC) patients remains to be ascertained. METHODS: One hundred and thirty-four consecutive cN+/BC-patients received NAC followed by SLN biopsy and axillary lymph node dissection. Cumulative incidence of overall (OS) and disease-free (DFS) survival, BC-related recurrences and death from BC were assessed using the Kaplan-Meier method both in the whole patient population and according to the SLN status. The log rank test was used for comparisons between groups. RESULTS: The SLN was identified in 123/134 (91.8%) patients and was positive in 98/123 (79.7%) patients. Sixty-five of them (66.3%) had other axillary nodes involved. SLN sensitivity and false-negative rate were 88.0% and 2.0%, Median follow-up was 10.2 years. Ten-year cumulative incidence of axillary, breast and distant recurrences, and death from BC were 6.5%, 11.9%, 33.4% and 31.3%, respectively. Ten-year OS and DFS were 67.3% and 55.9%. When stratified by SLN status, 10-year cumulative incidence of BC-related and loco-regional events, and death from BC were similar between disease-free SLN and micrometastatic SLN subgroups (28.9% vs 30.2%, p = 0.954; 21.6% vs 13.4%, p = 0.840; 12.9 vs 24.5%, p=0.494). Likewise, 10-year OS and DFS were comparable (80.0% vs 75.5%, p=0.975 and 68.0% vs 69.8, p=0.836). Both OS and DFS were lower in patients presenting a macrometastatic SLN (60.2% and 47.5%). CONCLUSION: Outcome of patients with micrometastatic SLN was similar to that of patients with disease-free SLN, which was more favorable as compared to that of patients with macrometastatic SLN.

Efficacy and Safety of Controlled Ovarian Stimulation With or Without Letrozole Co-administration for Fertility Preservation: A Systematic Review and Meta-Analysis.

Background: The co-administration of letrozole during controlled ovarian stimulation (COS) with gonadotropins is used to limit the potentially harmful effects of a supra-physiological rise in estrogen levels on hormone-sensitive cancers. However, the efficacy and safety of adding letrozole to COS remain debated. Methods: This is a systematic review and meta-analysis of published studies that compared the efficacy and safety of COS with co-administration of letrozole vs. COS without letrozole in all patient populations. A secondary analysis was done including only the studies in breast cancer patients. The primary efficacy endpoint was the number of retrieved mature Metaphase II (MII) oocytes. Secondary efficacy and safety endpoints were total number of oocytes, maturation rate, fertilization rate, number of cryopreserved embryos, peak estradiol levels, progesterone levels, and total gonadotropin dose. Data for each endpoint were reported and analyzed thorough mean ratio (MR) with 95% confidence interval (CI). Results: A total of 11 records were selected including 2,121 patients (990 patients underwent COS with letrozole and 1,131 COS without letrozole). The addition of letrozole to COS did not have any negative effect on the number of mature oocytes collected (MR = 1.00, 95% CI = 0.87-1.16; P = 0.967) and the other efficacy endpoints. COS with letrozole was associated with significantly decreased peak estradiol levels (MR = 0.28, 95% CI = 0.24-0.32; P < 0.001). Similar results were observed in the secondary analysis including only breast cancer patients. Conclusions: These findings are reassuring on the efficacy and safety of COS with gonadotropins and letrozole and are particularly important for fertility preservation in women with hormone-sensitive cancers.

Burning Questions in the Oncofertility Counseling of Young Breast Cancer Patients.

The improved prognosis of breast cancer patients makes survivorship issues an area of crucial importance. In this regard, an increased attention is needed toward the development of potential anticancer treatment-related long-term side-effects, including gonadal failure and infertility in young women. Therefore, fertility preservation and family planning are crucial issues to be addressed in all young women of reproductive age with newly diagnosed cancer. Despite a growing availability of data on the efficacy and safety of fertility preservation options and the fact that conceiving after prior history of breast cancer has become more accepted over time, there are still several gray zones in this field so that many physicians remain uncomfortable to deal with these topics. The purpose of this review is to answer some of the most controversial questions frequently asked by patients during their oncofertility counseling, in order to provide a detailed and up-to-date overview on the evidence available in this field to physicians involved in the care of young women with breast cancer.

LYMPHA Technique to Prevent Secondary Lower Limb Lymphedema.

BACKGROUND: Inguinofemoral lymphadenectomy carries a high risk of lower limb lymphedema. This report describes the feasibility of performing multiple lymphatic-venous anastomoses (MLVA) after inguinofemoral lymph node completion (LYMPHA technique) and the possible benefit of LYMPHA for preventing lymphedema. METHODS: Between February, 2011 and October, 2014, 11 patients with vulvar cancer and 16 patients with melanoma of the trunk requiring inguinofemoral lymphadenectomy underwent lymph node dissection and the LYMPHA technique. Blue dye was injected into the thigh 10 min before surgery. Lymphatics afferent to the blue nodes were used to perform MLVA using a collateral branch of the great saphenous vein. RESULTS: The mean age of patients in the vulvar cancer group was 52 years (range, 48-75 years). The melanoma group comprised seven men and nine women with a mean age of 41 years (range, 37-56 years). Of the 16 patients, 5 with vulvar cancer underwent bilateral inguinofemoral lymphadenectomy, whereas the remaining 6 patients with vulvar cancer and all 16 patients with melanoma of the trunk had unilateral node dissection. All the patients were treated by the LYMPHA technique. No lymphocele or infectious complications occurred. Transient lower-extremity edema occurred for one melanoma patient (6.25 %), which resolved after 2 months, and permanent lower-extremity edema occurred for one patient (9 %) with vulvar cancer. CONCLUSIONS: The LYMPHA technique appears to be feasible, safe, and effective for the prevention of lower limb lymphedema, thereby improving the patient's quality of life and decreasing health care costs.

Sentinel Lymph Node Biopsy Versus Axillary Dissection in Node-Negative Early-Stage Breast Cancer: 15-Year Follow-Up Update of a Randomized Clinical Trial.

BACKGROUND: Sentinel lymph node biopsy (SLNB) allows for staging of the axillary node status in early-stage breast cancer (BC) patients and avoiding complete axillary lymph node dissection (ALND) when the sentinel lymph node (SLN) is proven to be free of disease. In a previous randomized trial we compared SLNB followed by ALND (ALND arm) with SLNB followed by ALND only if the SLN presented metastasis (SLNB arm). At a mid-term of ≈ 6 years median follow-up, the two strategies appeared to ensure similar survival and locoregional control. We have revised these previous findings and update the results following a 15-year observation period. METHODS: Patients were randomly assigned to either the ALND or SLNB arm. The main endpoints were event-free survival (EFS), overall survival (OS), and axillary disease recurrence. EFS and OS were assessed using Kaplan-Meier analysis and the log-rank test. RESULTS: The ALND and SLNB arms included 115 and 110 patients, respectively. At 14.3 years median follow-up, 39 primary BC-related recurrences occurred, 22 (19 %) of which occurred in the ALND arm and 17 (16 %) occurred in the SLNB arm (p = 0.519). No axillary relapse developed in the SLNB arm, while two were observed in the ALND arm. OS (82.0 vs. 78.8 %) and EFS (72.8 vs. 72.9 %) were not statistically different between the ALND and SLNB arms (p = 0.502 and 0.953, respectively). CONCLUSIONS: SLNB is a safe and efficacious component of the surgical treatment of early-stage BC patients. In the long-term, SLNB is equivalent to ALND in terms of locoregional nodal disease control and survival in this subset of patients.

Lymphatic microsurgical preventing healing approach (LYMPHA) for primary surgical prevention of breast cancer-related lymphedema: over 4 years follow-up.

Breast cancer-related lymphedema (LE) represents an important morbidity that jeopardizes breast cancer patients' quality of life. Different attempts to prevent LE brought about improvements in the incidence of the pathology but LE still represents a frequent occurrence in breast cancer survivors. Over 4 years ago, Lymphatic Microsurgical Preventing Healing Approach (LYMPHA) was proposed and long-term results are reported in this study. From July 2008 to December 2012, 74 patients underwent axillary nodal dissection for breast cancer treatment together with LYMPHA procedure. Volumetry was performed preoperatively in all patients and after 1, 3, 6, 12 months, and once a year. Lymphoscintigraphy was performed in 45 patients preoperatively and in 30 also postoperatively after at least over 1 year. Seventy one patients had no sign of LE, and volumetry was coincident to preoperative condition. In three patients, LE occurred after 8-12 months postoperatively. Lymphoscintigraphy showed the patency of lymphatic-venous anastomoses at 1-4 years after operation. LYMPHA technique represents a successful surgical procedure for primary prevention of arm LE in breast cancer patients.