Diagnostic performance of image-guided vacuum-assisted breast biopsy after neoadjuvant therapy for breast cancer: prospective pilot study.

BACKGROUND: Image-guided vacuum-assisted breast biopsy (VABB) of the tumour bed, performed after neoadjuvant therapy, is increasingly being used to assess residual cancer and to potentially identify to identify pathological complete response (pCR). In this study, the accuracy of preoperative VABB specimens was assessed and compared with surgical specimens in patients with triple-negative or human epidermal growth factor receptor 2 (HER2)-positive invasive ductal breast cancer after neoadjuvant therapy. As a secondary endpoint, the performance of contrast-enhanced MRI of the breast and PET-CT for response prediction was assessed. METHODS: This single-institution prospective pilot study enrolled patients from April 2018 to April 2021 with a complete response on imaging (iCR) who subsequently underwent VABB before surgery. Those with a pCR at VABB were included in the primary analysis of the accuracy of VABB. The performance of imaging (MRI and PET-CT) was analysed for prediction of a pCR considering both patients with an iCR and those with residual disease at postneoadjuvant therapy imaging. RESULTS: Twenty patients were included in the primary analysis. The median age was 44 (range 35-51) years. At surgery, 18 of 20 patients showed a complete response (accuracy 90 (95 per cent exact c.i. 68 to 99) per cent). Only two patients showed residual ductal intraepithelial neoplasia of grade 2 and 3 respectively. In the secondary analysis, accuracy was similar for MRI and PET-CT (77 versus 78 per cent; P = 0.76). CONCLUSION: VABB in patients with an iCR might be a promising method to select patients for de-escalation of surgical treatment in triple-negative or HER2-positive breast cancer. The present results support such an approach and should inform the design of future trials on de-escalation of surgery.

A New Level II Oncoplastic Technique for Inferior Pole Defects: The Three-Petal Glandular Reconstruction (3-PR).

INTRODUCTION: Oncoplastic surgery (OPS) allows wide excisions and accurate tumor resection and reduces breast deformities by immediate reconstruction of large defects. Superior pedicled mammaplasties allow excellent results in large breasts. Conversely, loco-regional flaps are the standard of care in small-to-medium breasts. However, both techniques show limitations in case of large resections of the lower pole, resulting in skin retraction and downward deviation of nipple and areola. We present a new technique for inferior pole reconstruction to overcome these limitations. It is called "the three-petal reconstruction" (3-PR). METHODS: Between September 2016 and May 2019, ten patients with invasive breast cancer of the lower pole underwent breast conservation and 3-PR. RESULTS: The 3-PR was uneventful in all patients. No major or minor complications were recorded. Patient and surgeon evaluations scored as good to excellent in all cases. Surveillance examinations in the follow-up did not reveal calcifications nor any findings of suspicion within the reconstructed area. CONCLUSIONS: In case of very large defect of lower pole, the 3-PR reveals to be an easy, fast, reproducible method for inferior pole reconstruction. It can represent a niche between therapeutic mammaplasty and perforator flaps, and it could be added to existing available options for tailored reconstruction. 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 .

The use of indocyanine green as the only tracer for the identification of the sentinel lymph node in breast cancer: safety and feasibility.

Background: Sentinel lymph node biopsy (SLNB) is now considered the "gold standard" for axillary staging in the treatment of breast cancer. Most of the lymph node mapping experiences have been performed with a radioisotope (albumin-Tc99m) associated or not with the intraoperative injection of a dye, such as Patent-Blue V. Recent studies have shown how the use of indocyanine green (ICG; a drug used for diagnostic use for many years in other sectors) as a fluorescent tracer, allows to obtain alone detection rate of the sentinel lymph node similar or even better, without the risks related to radioactivity and with better use of resources. Methods: From March 2020 to February 2021, 184 patients with breast cancer cN0, candidate for SLNB were enrolled at the Complex Operative Unit (UOC) of Breast Surgery, Breast Unit of the Hospital of Verona. The ICG was injected into the periareolar site and was used the NOVADAQ SPY Elite system (Stryker®) for transcutaneous intraoperative observation of fluorescence. The primary objective of the study is the evaluation of the feasibility of the technique and its sensitivity in the identification of sentinel lymph node; among the secondary endpoints the recognition of predictive factors on the identification (t1-t0) and extraction (t2-t1) times of the sentinel lymph node, and on the number of lymph node uptake pathways. Finally, was analyse the safety of the technique. Results: The sentinel lymph node was detected and removed in 98.3%. The average number of sentinel lymph nodes extracted is 1.527, while the average number of total lymph nodes (TLNs) extracted is 3.375. The sensitivity of the sentinel lymph node detection technique with ICG, turns out to be 100%. Finally, in the literature, lymphatic function decreases with increasing age, reducing the identification rate of the SLN; this is not confirmed in our study. Conclusions: Our study confirms the use of the only ICG tracer for SLNB in cN0 breast cancer, demonstrating that it is a safe, effective and sensitive technique, which also allows to reduce costs, risks and organizational efforts.

A Randomized Trial of Robotic Mastectomy Versus Open Surgery in Women With Breast Cancer or BrCA Mutation.

OBJECTIVE: The aim of this study was to compare robotic mastectomy with open classical technique outcomes in breast cancer patients. SUMMARY BACKGROUND DATA: As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic, and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages, and dangers. METHODS: In a phase III, open label, single-center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. RESULTS: Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy versus open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy, whereas they significantly decreased after open procedure (P < 0.02). The overall Body Image Scale questionnaire score was 20.7 ±â€Š13.8 versus 9.9 ±â€Š5.1 in the robotic versus open groups respectively, P < 0.0001. At median follow-up 28.6months (range 3.7-43.3), no local events were observed. CONCLUSIONS: Complications were similar among groups upholding the robotic technique to be safe. Quality of life was maintained after robotic mastectomy while significantly decrease after open surgery. Early follow-up confirm no premature local failure.ClinicalTrials.gov NCT03440398.

Breast conservative surgery and whole breast radiotherapy versus breast conservative surgery and IORT: surgical opinion.

BACKGROUND: To define the possibility of intraoperative radiation therapy (IORT)'s application on clinical practice and point out the problems observed by Verona Breast Unit. METHODS: Among the patients of the Breast Unit at Azienda Ospedaliera Universitaria Integrata of Verona, treated between July 2015 and June 2017, were identified 459 patients undergoing breast conserving surgery for a carcinoma, followed by IORT in 77 cases or by Whole Breast Radiotherapy (WBRT) in 382 cases. The data of WBRT group were analyzed considering IORT eligibility criteria to identify a sub-group of eligible patients, for whom we evaluated the diagnostic process that had led to exclusion from IORT. RESULTS: In WBRT group 184 patients (48%) had a ductal NOS infiltrating carcinoma, of which 64 cases (16.8%) were eligible for IORT. Other 79 patients of WBRT group (21%) presented DCIS, of which only 27 were in the American Society for Radiation Oncology "suitable" group for IORT. Considering the results of the preoperative exams, or rather needle biopsy and MRI scan, 55 patients of 64 (85.9%) resulted unsuitable for IORT, while nine patients (14.1%) could be eligible. CONCLUSIONS: IORT's major limits are: the restricted eligibility criteria, especially on histology; the need of a complete execution of preoperative exams and the technical limits of these exams. ASTRO suitable group, including small diameter, low-grade DCIS, might be used to extend the eligibility criteria. A multidisciplinary approach might improve the preoperative study, so the use of IORT in clinical practice.

Economic implications of ACOSOG Z0011 trial application into clinical practice at the European Institute of Oncology.

BACKGROUND AND OBJECTIVES: The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. PATIENTS AND METHODS: We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). RESULTS: Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. CONCLUSIONS: Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

Is Nipple-Sparing Mastectomy Indicated after Previous Breast Surgery? A Series of 387 Institutional Cases.

BACKGROUND: Previous breast surgery does not represent an absolute contraindication for nipple-sparing mastectomy, although it may negatively interfere with surgical outcomes. The aim of the authors' study was to confirm the feasibility of nipple-sparing mastectomy after previous breast surgery, focusing on skin incisions and risk factors, complications, and oncologic outcomes. METHODS: The authors retrospectively identified 368 patients who underwent 387 nipple-sparing mastectomies and reconstruction after previous surgery (quadrantectomy, breast resection, augmentation and reduction mammaplasty, mastopexy) at the European Institute of Oncology from January of 2003 to November of 2017. Patterns of skin incisions (i.e., radial, hemiperiareolar, periareolar, vertical pattern, inframammary fold, Wise-pattern, and round-block) for primary surgery and for mastectomy, type of reconstruction, and radiotherapy have been recorded. The authors collected data regarding early and late complications and further operations (implant change, fat grafting) performed within 2 years to improve cosmetic outcomes. Oncologic follow-up has been reported for in-breast recurrences. RESULTS: Complete and partial nipple-areola complex necrosis occurred, respectively, in 2.8 percent and in 5.4 percent of cases. The authors recorded 5.4 percent failures resulting in implant removal. The analysis of risk factors for complications or for the need for further operations showed no significant association with skin incision for first surgery and mastectomy, use of the same skin incision, previous radiotherapy, or type of primary surgery. Five-year overall survival and disease-free survival were 99.1 and 93.8 percent, respectively. No nipple recurrence was recorded. CONCLUSIONS: The authors' results confirm that nipple-sparing mastectomy can be a safe surgical procedure after previous breast surgery. Surgical planning should be tailored to each patient. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Long-term outcome and axillary recurrence in elderly women (≥70 years) with breast cancer: 10-years follow-up from a matched cohort study.

BACKGROUND AND OBJECTIVES: The oncological benefit of axillary surgery (AS), with sentinel lymph node biopsy (SLNB) or axillary dissection (ALND), in elderly women affected by breast cancer (BC) is controversial. We evaluated AS trends over a 10-year follow-up period as well as locoregional and survival outcomes in this subset of patients. METHODS: Patients aged 70 years or older, treated between 1994 and 2008, were selected and divided in two groups, depending on whether or not AS was performed. A (1:1) matched analysis for all relevant clinicopathological features was performed. Outcomes were analyzed using the Kaplan-Meier method and univariate Cox-proportional hazard ratio analysis. RESULTS: A total of 1.748 patients were identified and stratified by age (70-74, 75-79, 80-84). A matched analysis was performed for 252 patients: 122 who underwent AS and 122 who did not. At 10-year follow-up, ipsilateral breast tumor recurrence, distant metastasis and contralateral BC were similar, p = 0.83, p = 0.42 and p = 0.28, respectively. In the no-AS group, a significant increased risk of axillary lymph-node recurrence was identified at 5- and confirmed at 10-years (p = 0.038), without impact on overall survival at 5- and 10-years (p = 0.52). In the non-AS group, higher rate of axillary recurrence at 10-years was observed in patients with poorly differentiated (24.1%, 95% CI 7.2-46.2), highly proliferative (Ki67 ≥ 20%: 17.1%, 95% CI 0.6-33.3) and luminal B tumors (16.8%, 95% CI 5.9-35.5). CONCLUSIONS: Axillary staging in elderly women does not impact long-term survival. Tailoring surgery according to tumor biology and age may improve locoregional outcome.

Metaplastic breast cancer: Prognostic and therapeutic considerations.

INTRODUCTION: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. METHODS: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). RESULTS: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. CONCLUSION: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

A Novel Method of Implant Coverage for Post-Mastectomy Reconstruction after Previous Augmentation: A Case Report.

BACKGROUND: Breast augmentation is the most common -cosmetic surgical procedure in the USA, with nearly 300,000 women undergoing surgery annually. National incidence rates predict that among women undergoing breast augmentation each year, approximately 35,000 will eventually be diagnosed with breast cancer, in particular individual BRCA1/2 germline mutant carriers. CASE REPORT: Our case introduces a novel method of implant coverage after immediate post-mastectomy reconstruction in augmented patients. A novel "capsular flap" (flap of the pre-existing old capsule) is isolated and refolded to cover the outer lower portion of the implant. CONCLUSION: Tailored surgical approaches can be offered to those patients previously augmented and requiring mastectomy after breast cancer diagnosis.

Transumbilical Single-port Robotically Assisted Nipple-sparing Mastectomy: A Cadaveric Study.

The authors performed a transumbilical, single-port robotically assisted, nipple-sparing mastectomy on a cadaveric model to assess technical feasibility. Surgeon-controlled, robotic-wristed instrumentation, as well as 3-dimensional high definition (HD) vision allowed the entire dissection to be performed through a single incision placed in the umbilicus. The technique warrants further exploration and development before any application in clinical applied research.

Multicentric breast cancer with heterogeneous histopathology: a multidisciplinary review.

Multiple synchronous (multifocal or multicentric) ipsilateral breast cancers with heterogeneous histopathology are a rare clinical occurrence, however, their incidence is increasing due to the use of MRI for breast cancer screening and staging. Some studies have demonstrated poorer clinical outcomes for this pattern of breast cancer, but there is no evidence to guide clinical practice. In this multidisciplinary review, we reflect on pathology and molecular characteristics, imaging findings, surgical management including conservation and reconstructive options and approach to the axilla, and the role of chemotherapy and radiotherapy. Multidisciplinary discussions appear decisive in planning an appropriate surgical choice and defining the correct systemic treatment tailored to each clinical condition.

Validation of a Novel Nomogram for Prediction of Local Relapse after Surgery for Invasive Breast Carcinoma.

BACKGROUND: Around 7% of women who undergo breast-conserving surgery (BCS) or mastectomy are at risk of developing ipsilateral breast tumor recurrence (IBTR). When assessing risks that, like that of IBTR, depend on multiple clinicopathological variables, nomograms are the predictive tools of choice. In this study, two independent nomograms were constructed to estimate the individualized risk of IBTR after breast surgery. PATIENTS AND METHODS: In this retrospective study, 18,717 consecutive patients with primary invasive breast cancer were enrolled. The training set used for building the nomograms comprised 15,124 patients (11,627 treated with BCS and 3497 with mastectomy), while the validation set included 3593 women (2565 BCS and 1028 mastectomy). Median follow-up time was 8 years in the training set and 6 years in the validation set. Multivariable Cox proportional hazards regression was used to identify independent factors for IBTR. Two separated nomograms were constructed on multivariate models for BCS and mastectomy. RESULTS: The factors that associated with IBTR after either BCS or mastectomy were identified. The two multivariable models were used to build nomograms for the prediction of IBTR 1 year, 5 years, and 10 years after BCS or after mastectomy. Five-year and 10-year IBTR rates in the BCS training set were equal to 3.50% and 7.00%, respectively, and to 5.39% and 7.94% in the mastectomy training set. The nomograms were subsequently validated with c-index values of 0.77 and 0.69 in the BCS and mastectomy validation sets, respectively. CONCLUSIONS: The nomograms presented in this study provide clinicians and patients with a valuable decision-making tool for choosing between different treatment options for invasive breast cancer.

Update on the Feasibility and Progress on Robotic Breast Surgery.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however, data regarding the feasibility and safety of the procedure are limited. OBJECTIVE: The aim of this study was to present and discuss perioperative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019. METHODS: Patients underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Perioperative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence-free, disease-free, and overall survival were analyzed. RESULTS: Overall, 73 women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 h and 32 min. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring reoperation was 4.3%, and the rate of flap or nipple necrosis was 1.1%. Median follow-up was 19 months (range 3.1-44.8). No local recurrences occurred. Overall survival at 12, 24, or 60 months was 98% (95% confidence interval 86-100%). CONCLUSION: We observed a low complication rate in 94 consecutive RNSM procedures, demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.

Multidisciplinary management of CDH1 germinal mutation and prophylactic management hereditary lobular breast cancer: A case report.

INTRODUCTION: Germline CDH1 mutations, classically associated with hereditary diffuse gastric cancer (HDGC), also imply an increased lifetime risk of developing lobular breast cancer (LBC) in a highly penetrant autosomal dominant manner. PRESENTATION OF CASE: We report a 44-year-old woman CDH1 mutation carrier with a strong family history of cancer, who previously had prophylactic total gastrectomy. We registered normal findings at the breast and axilla assessment. Mammography, ultrasonography and breast MRI scans were negative for cancer. In our Institute a bilateral prophylactic mastectomy followed by breast reconstruction was performed. Foci of atypical lobular hyperplasia(ALH) and lobular carcinoma in situ (LCIS) were histologically shown. DISCUSSION: The current consensus guidelines for women with pathogenic CDH1 mutations recommend annual mammography, ultrasound, breast MRI scans and clinical breast examination starting at the age of 35. Due to the well-documented aggressive behavior of this particular type of cancer, bilateral mastectomy and reconstruction would be more beneficial for this kind of high-risk patients. CONCLUSION: Conflicting evidences and lacking data about the benefits in terms of overall survival, disease-free survival and the long-term outcomes related to prophylactic bilateral mastectomy for CDH1 mutation carriers restrict the instruction for this type of procedure to selected cases, which should always be managed by a multidisciplinary team.

Breast cancer and neoadjuvant chemotherapy: indications for and limits of breast-conserving surgery.

AIM: The aim of our study was to determine how many and what subtypes of breast cancer could be treated with breast-conserving surgery after NACT. Another outcome was to determine the applicability of MD Anderson Cancer Center nomogram to predict it. MATERIAL OF STUDY: We reviewed the histological examinations of 86 performed mastectomies according to the indications to BCS after NACT. For 73 cases, collected all the necessary data, we could use the nomogram available on the MDACC website to calculate the probability of BCS and pCR. RESULTS: In our experience the BCS rate would increase by 34,1%, from 3,7% to 3.,8%. Patients with Triple Negative and HER2+, ER- more than ER+, show higher rates of pCR and BCS. The MDACC nomogram predicts accurately the probability of pCR and BCS after NACT in HER2 negative cancers but not in HER2 positive ones treated with Trastuzumab. This suggests that a specific nomogram for HER2 positive carcinomas has to be developed. CONCLUSION: BCS after NACT is feasible and safe in terms of LRR, DFS and OS, if patients are properly studied and selected. Indication to BCS after NACT needs of a multidisciplinary assessment considering clinical staging, biological characteristics, the radiological response pattern and the expected concordance between imaging and histology. KEY WORDS: Breast Cancer, Breast-conserving surgery, Neoadjuvant chemotherapy.

Breast cancer and gastrointestinal metastasis. A case report and review of the literature.

INTRODUCTION: Invasive lobular cancer (ILC) is the second most common type of a heterogeneous group of different histological types of invasive breast carcinoma. Breast cancer can metastatize anywhere, the most common sites are bones, liver, lungs and brain. Gastrointestinal tract (GI) metastases observed in autopsy studies account for about 6% to 18% of the overall metastases from breast cancer. OBJECTIVE: We describe a 54-year old woman with recurrent ILC in the contralateral breast. She underwent right mastectomy 16 years before. After symptomatic presentation a duodenal invasion was found and subjected to diagnostic scrutiny (FDG PET/CT, diagnostic CT, MR, EGDS). In particular, we analyse if FDG PET/CT is enough accurate in the restaging of the patient. A review of our database and of the literature of similar cases were made. RESULTS: In this patient CT and RM were suspicious for a slow developing process of the duodenum but FDG PET/CT did not show pathological uptake in the affected duodenal tract. A highly intense focus was described in a cervical lymph node, that there isn't metastatic lesion, whereas the recurrent breast lesion had only slight increased glycolytic activity. CONCLUSION: Metastatic lobular carcinoma of the breast is a rare entity with a heterogeneous range of clinical presentations. Detection of eventual gastrointestinal metastases are complicated to assess. ILC has various scale of glycolytic activity both in the primary lesion as well in the metastatic foci. When the level of suspicion is high and there is no uptake of FDG, further investigations are necessary. KEY WORD: Abdominal metastasis, FGD PET-TC, Lobular Breast Cancer.

[18F]FDG PET/CT features for the molecular characterization of primary breast tumors.

PURPOSE: The aim of this study was to evaluate the role of imaging features derived from [18F]FDG-PET/CT to provide in vivo characterization of breast cancer (BC). METHODS: Images from 43 patients with a first diagnosis of BC were reviewed. Images were acquired before any treatment. Histological data were derived from pretreatment biopsy or surgical histological specimen; these included tumor type, grade, ER and PgR receptor status, lymphovascular invasion, Ki67 index, HER2 status, and molecular subtype. Standard parameters (SUVmean, TLG, MTV) and advanced imaging features (histogram-based and shape and size features) were evaluated. Univariate analysis, hierarchical clustering analysis, and exact Fisher's test were used for statistical analysis of data. Imaging-derived metrics were reduced evaluating the mutual correlation within group of features as well as the mutual correlation between groups of features to form a signature. RESULTS: A significant correlation was found between some advanced imaging features and the histological type. Different molecular subtypes were characterized by different values of two histogram-based features (median and energy). A significant association was observed between the imaging signature and luminal A and luminal B HER2 negative molecular subtype and also when considering luminal A, luminal B HER2-negative and HER2-positive groups. Similar results were found between the signature and all five molecular subtypes and also when considering the histological types of BC. CONCLUSIONS: Our results suggest a complementary role of standard PET imaging parameters and advanced imaging features for the in vivo biological characterization of BC lesions.