The Prediction Analysis of Microarray 50 (PAM50) Gene Expression Classifier Utilized in Indeterminate-Risk Breast Cancer Patients in Hungary: A Consecutive 5-Year Experience.

BACKGROUND: Breast cancer has been categorized into molecular subtypes using immunohistochemical staining (IHC) and fluorescence in situ hybridization (FISH) since the early 2000s. However, recent research suggests that gene expression testing, specifically Prosigna® Prediction Analysis of Microarray 50 (PAM50), provides more accurate classification methods. In this retrospective study, we compared the results of IHC/FISH and PAM50 testing. We also examined the impact of various PAM50 parameters on overall survival (OS) and progression-free survival (PFS). RESULTS: We analyzed 42 unilateral breast cancer samples, with 18 classified as luminal A, 10 as luminal B, 8 as Human epidermal growth factor receptor 2 (HER2)-positive, and 6 as basal-like using PAM50. Interestingly, 17 out of the 42 samples (40.47%) showed discordant results between histopathological assessment and the PAM50 classifier. While routine IHC/FISH resulted in classification differences for a quarter to a third of samples within each subtype, all basal-like tumors were misclassified. Hormone receptor-positive tumors (hazard rate: 8.7803; p = 0.0085) and patients who had higher 10-year recurrence risk scores (hazard rate: 1.0539; p = 0.0201) had shorter OS and PFS. CONCLUSIONS: Our study supports the existing understanding of molecular subtypes in breast cancer and emphasizes the overlap between clinical characteristics and molecular subtyping. These findings underscore the value of gene expression profiling, such as PAM50, in improving treatment decisions for breast cancer patients.

Tailored axillary surgery in patients with clinically node-positive breast cancer: Pre-planned feasibility substudy of TAXIS (OPBC-03, SAKK 23/16, IBCSG 57-18, ABCSG-53, GBG 101).

AIM: We developed tailored axillary surgery (TAS) to reduce the axillary tumor volume in patients with clinically node-positive breast cancer to the point where radiotherapy can control it. The aim of this study was to quantify the extent of tumor load reduction achieved by TAS. METHODS: International multicenter prospective study embedded in a randomized trial. TAS is a novel pragmatic concept for axillary surgery de-escalation that combines palpation-guided removal of suspicious nodes with the sentinel procedure and, optionally, imaging-guided localization. Pre-specified study endpoints quantified surgical extent and reduction of tumor load. RESULTS: A total of 296 patients were included at 28 sites in four European countries, 125 (42.2%) of whom underwent neoadjuvant chemotherapy (NACT) and 71 (24.0%) achieved nodal pathologic complete response. Axillary metastases were detectable only by imaging in 145 (49.0%) patients. They were palpable in 151 (51.0%) patients, of whom 63 underwent NACT and 21 had residual palpable disease after NACT. TAS removed the biopsied and clipped node in 279 (94.3%) patients. In 225 patients with nodal disease at the time of surgery, TAS removed a median of five (IQR 3-7) nodes, two (IQR 1-4) of which were positive. Of these 225 patients, 100 underwent ALND after TAS, which removed a median of 14 (IQR 10-17) additional nodes and revealed additional positive nodes in 70/100 (70%) of patients. False-negative rate of TAS in patients who underwent subsequent ALND was 2.6%. CONCLUSIONS: TAS selectively reduced the tumor load in the axilla and remained much less radical than ALND.

Assessing the needs of Hungarian breast cancer patients for modern oncoplastic breast surgical treatment. Questionnaire study of 500 patients / A magyar emlorákos betegek igényei a korszeru onkoplasztikus emlosebészeti ellátásra. 500 beteg kérdoíves vizsgálata

INTRODUCTION: The significant need for breast reconstruction resulting from the spread of oncoplastic breast surgery raises a number of systemic issues. Clarification and regulation of the indications are needed for aesthetic changes of the reconstructed breast due to oncotherapy treatments, ageing and technical problems of implants; a number of operations, targeted aesthetic goals as well as surgical capacities and financial background should also be determined. AIM: Our aim was to conduct a survey on the opinions and needs of the Hungarian breast cancer population about a modern breast reconstruction system. PATIENT AND METHOD: A study was conducted enrolling 500 patients who underwent mastectomy with immediate or delayed reconstruction. A structured questionnaire containing eleven questions was used to measure the attitude for loss and reconstruction of breast, the expectation of cosmetic outcome and qualification of the operating surgeon and the needs relating to the health system and funding. RESULTS: The median age was 47 years (min.-max.: 26-73), 59% (n = 294) was married and 52% (n = 260) had graduated in university. The majority of women (70%; n = 348) would like to have nakedly also similar breasts after the reconstruction process. To achieve this, 43% (n = 217) and 37% (n = 184) would undergo maximum two or four procedures, respectively, supported by the national health insurance company. 86% (n = 430) would like to choose qualified breast surgeon for her treatment. CONCLUSION: The modern oncoplastic treatment raises complex, systemic issues. Women with breast cancer would like to have qualified breast surgeons restoring their breasts by two operations, all funded by the national health insurance company. Orv Hetil. 2020; 161(29): 1221-1228.

Evaluation of the modified Regnault "B" technique as a standard level II oncoplastic breast-conserving surgery / A módosított Regnault "B" emlomegtartó mutét mint II. szintu standard onkoplasztikus emlosebészeti technika

INTRODUCTION AND AIM: This study aimed to describe the modified Regnault "B" oncoplastic technique as a standard volume-displacement level II oncoplastic breast-conserving surgery and the related clinicopathological study. METHOD: A retrospective, single-centre study was performed between April 2012 and October 2018 involving 215 breast-cancer patients. Patient characteristics and postoperative complications were recorded, and the quality of life was rated by questionnaires. Aesthetic outcomes were evaluated with BCCT.core software and a five-point Likert scale. RESULTS: The mean patient age was 53 years (range: 29-81 years), with a median follow-up of 47 months (range: 7-85 months). The average surgery time was 47 min (range: 35-85 min) and the pathological average size of the tumours was 33 mm (range: 18-58 mm). Due to positive surgical margins, 13 (6%) completion re-excisions and 3 (1.4%) mastectomies were performed. In total, 16 complications (7.4%) were recorded. The median Likert scale score was 4.2, and the median overall aesthetic outcome assessed by BCCT.core was 1.3 points. According to the quality of life questionnaire, average points of the results demonstrated a high level of patient satisfaction. CONCLUSION: In medium- to large-breasted patients, the modified Regnault "B" technique is a safe and repeatable level II volume-displacement oncoplastic breast-conservation technique. This technique allows extended removal (20-50% of breast tissue) of T1-T3 tumours from the upper outer quadrant and the border of outer quadrants of the breast with improved aesthetic results. The advantage of this technique is that contralateral symmetrisation is not required, while disadvantage of this technique is the skin incision on the breast skin envelope that can make some difficulties when completion mastectomy is required with immediate reconstruction. Orv Hetil. 2020; 161(24): 1002-1011.

Long-Term Dynamic Changes in Cosmetic Outcomes and Patient Satisfaction after Implant-Based Postmastectomy Breast Reconstruction and Contralateral Mastopexy with or without an Ultrapro Mesh Sling Used for the Inner Bra Technique. A Retrospective Correlational Study.

Immediate implant-based postmastectomy breast reconstruction (IPMBR) with contralateral symmetrization has mostly short-term limited evidence of cosmetic outcomes. Because 84% of early-stage breast cancer patients have overall survival of more than 10 years, reconstructed breast symmetry should provide long-lasting results and acceptable patient satisfaction. Ageing, changes in body weight, and biomechanical changes after IPMBR and symmetrization may contribute to symmetry worsening. This non-interventional single-centre retrospective correlational study presents the clinical and aesthetic results of synthetic ULTRAPRO® mesh inner bra sling.

Evaluation of the central pedicled, modified Wise-pattern technique as a standard level II oncoplastic breast-conserving surgery: A retrospective clinicopathological study of 190 breast cancer patients.

Involving 207 breast cancer patients a retrospective study was performed to facilitate the acceptance of the central pedicled, modified Wise-pattern therapeutic mammoplasty technique as a standard volume-displacement level II oncoplastic breast-conserving surgery (OBCS). The overall local recurrence rate was 5.8% with an average follow-up of 43.9 months. The median time to the initiation of the adjuvant treatment was 4.9 weeks. Due to positive surgical margins, 13 (6.84%) completional surgeries were performed. In total, 45 complications (12.9%) were recorded. The median values of the esthetic outcomes represented improved cosmetic results. The modified Wise-pattern technique could be a standard, safe and repeatable level II volume-displacement OBCS.

A long-term retrospective comparative study of the oncological outcomes of 598 very young (≤35 years) and young (36-45 years) breast cancer patients.

BACKGROUND: Breast cancer diagnosed in very young women (VYWBC; ≤35 years) and young women (YWBC; 36-45 years) tends to be heterogeneous. The current study aimed to compare the clinicopathological characteristics and long-term clinical outcomes between YWBC and VYWBC subgroups. PATIENTS AND METHODS: The institutional prospectively led database was retrospectively analysed from 2000 to 2014 at the National Institute of Oncology, Hungary. A total of 297 patients were assigned to the VYWBC group, and 301 patients were assigned to the YWBC group. RESULTS: The median follow-up period was 69 months for the VYWBC group and 79 months for the YWBC group. Significant differences were observed based on breast cancer subtype. The proportion of Triple-negative and ER-negative patients was higher in the VYWBC group than in the YWBC group (P = 0.00008). The incidence of distant metastasis was significantly higher in the VYWBC group (P = 0.01). Significant differences in the frequency of chemotherapy (P = 0.049) and endocrine therapy (P = 0.037) were observed between the two groups. The YWBC group exhibited significantly better overall survival (OS) and disease-free survival (DFS) rates than did the VYWBC group (P = 0.00005 and P = 0.00004, respectively). CONCLUSION: Breast cancers in VYWBC are biologically different from those in YWBC and tend to be more aggressive. Younger age was associated with worse OS and DFS. Young women with breast cancer should be subgrouped into VYWBC and YWBC populations, and these subgroups should be targeted by specialized clinical trials and further investigations.

Evaluation of a Retroglandular Oncoplastic Technique as a Standard Level I Oncoplastic Breast-Conserving Surgery: A Retrospective Clinicopathologic Study of 102 Patients With Breast Cancer.

BACKGROUND: This study presents a novel Level I oncoplastic breast-conserving surgery technique for performing tumorectomy by retroglandular exploration through a skin incision made in the inferior mammary fold. PATIENTS AND METHODS: A retrospective single-center cohort study involving patients with early-stage breast cancer (n = 102) was performed. The patient characteristics were recorded, as well as the quality of life rated by BREAST-Q. Postoperative complications were assessed using the Clavien-Dindo classification system. Esthetic outcomes were evaluated with Breast Cancer Conservative Treatment-cosmetic results (BCCT.core) software and a 5-point Likert scale. RESULTS: The median follow-up time was 11 months (range, 7-25 months). The median specimen weight and operative time were 49.8 g (range, 13.4-117.9 g) and 40 minutes (range, 20-80 minutes), respectively. The mean pathologic tumor size was 15 mm (SD, ±7). Owing to positive surgical margins, re-excisions and mastectomies were performed in 13.7% and 2.9% of patients, respectively. The overall complication rate was 24.5% (n = 25), with the most common being seroma formation (13.7%; n = 14). The median Likert scale score was 4.3 (range, 2.1-5), and the median overall esthetic outcome assessed by BCCT.core was 2.1 points (range, 1-4 points). In BREAST-Q domains, the median scores of the "adverse effects of radiation," "physical well-being," the "satisfaction with breasts," and the "psychosocial well-being" were 27, 35, 90, and 93, respectively. CONCLUSION: Retroglandular oncoplastic breast-conserving surgery is a novel, effective Level I oncoplastic technique for radical resection of breast tumors ≤ 3 cm in size. Additional advantages include the preservation of natural breast shape, the safety of the technique, and the lack of a need for contralateral symmetrization.

Second breast-conserving surgery and interstitial brachytherapy vs. salvage mastectomy for the treatment of local recurrences: 5-year results.

PURPOSE: The purpose of this study was to report the clinical outcomes of a second breast-conserving therapy (2nd BCT) with perioperative interstitial brachytherapy (iBT) vs. those of salvage mastectomy (sMT) in the treatment of ipsilateral breast tumor recurrences (IBTRs). METHODS AND MATERIALS: Between 1999 and 2015, 195 patients with IBTR after a previous breast-conserving treatment were salvaged either with reexcision and perioperative high-dose-rate iBT (n = 39), or with sMT (n = 156). In the 2nd BCT group, a total dose of 22 Gy in five fractions of 4.4 Gy was delivered to the tumor bed with intraoperatively implanted catheters for 3 consecutive days. RESULTS: The median followup time was 59 months (1-189) in the 2nd BCT, and 56 months (3-189) in the sMT group. The mean size of IBTR was 16 mm (2-70) vs. 24 mm (2-90), respectively (p = 0.0005), but there were no other significant differences in patient- or IBTR-related parameters between the two groups. During the followup period, 4 of 39 (10.2%) and 28 of 156 (17.9%) second local recurrences (2nd LR) occurred in the 2nd BCT and the sMT group, respectively. The 5-year actuarial rate of 2nd LR was 6% vs. 18% (p = 0.22), the 5-year probability of disease-free, cancer-specific and overall survival was 69% vs. 65% (p = 0.13), 85% vs. 78% (p = 0.32), and 81% vs. 66% (p = 0.15), respectively. In the 2nd BCT group, the rate of good to excellent cosmesis was 70%. CONCLUSIONS: 2nd BCT with perioperative high-dose-rate iBT is a safe and feasible option for the management of IBTR, resulting in similar 5-year oncological outcomes and better cosmetic results compared with sMT.

Comparison of clinicopathologic, cosmetic and quality of life outcomes in 700 oncoplastic and conventional breast-conserving surgery cases: A single-centre retrospective study.

INTRODUCTION: Limited data is available from studies that directly compare oncoplastic breast surgery and conventional breast-conserving surgery (CBCS) procedures. The aim of this study was to compare three volume displacement oncoplastic breast-conserving surgery (OBCS) techniques to CBCS procedures, providing more evidence and facilitating the standardization of OBCS techniques. PATIENTS AND METHODS: A retrospective single-centre comparative study was performed between January 2010 and January 2017 involving 758 breast cancer patients. The endpoints for comparison were oncological safety, frequency of complications, initiation time of adjuvant therapy, aesthetic outcome, quality of life and operation time. To compare data, statistical analyses were performed. RESULTS: The mean follow-up time was 51 months for the OBCS group and 52 months for the CBCS group. The excised weight of the specimens was significantly larger in the OBCS group than in the CBCS group (90 g vs. 63 g). The overall complication rate (5.7% vs. 6.6%), the initiation time of adjuvant therapy (4.2 weeks vs. 4.1 weeks) and the local recurrence rate (2.0% vs. 3.7%) did not differ significantly. Scores for the aesthetic outcome were significantly higher in the OBCS group; however, required longer operation time. CONCLUSION: The investigated OBCS procedures allowed the removal of large volumes of breast tissue with improved cosmetic outcomes without delay in adjuvant therapies, maintaining the oncological safety. However, OBCS required longer operation time. Furthermore, the extended radicality of the OBCS could reduce the rate of re-excision and completion mastectomy, although it may result in the overtreatment of some breast cancer patients.

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

AIM OF THE STUDY: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. MATERIALS AND METHODS: As a novel approach, we investigated B cells infiltrating breast carcinomas and melanomas (TIL-B) in terms of their tumour antigen binding potential. By developing the TIL-B phage display technology we provide here a new technology for the specific detection of highly tumour-associated antigens. Single chain Fv (scFv) antibody fragment phage ELISA, immunofluorescence (IF) FACS analysis, chamber slide technique with IF confocal laser microscopy and immunohistochemistry (IHC) in paraffin-embedded tissue sections were set up and standardized. RESULTS: We showed strong tumour-associated disialylated glycosphingolipid expression levels on various cancer cells using scFv antibody fragments, generated previously by uniquely invasive breast carcinoma TIL-B phage display library technology. CONCLUSIONS: We report herein a novel strategy to obtain antibody fragments of human origin that recognise tumour-associated ganglioside antigens. Our investigations have the power to detect privileged molecules in cancer progression, invasiveness, and metastases. The technical achievements of this study are being harnessed for early diagnostics and effective cancer therapeutics.

Barriers to Organized Mammography Screening Programs in Hungary: A Questionnaire-based Study of 3,313 Women.

BACKGROUND/AIM: Despite well-organized Hungarian invitational mammography screening, participation rates have never reached 50%. This is similar to rates in Central Eastern Europe. In order to reduce breast cancer mortality, the participation rate should be at least 70%. This questionnaire-based study assessed the barriers associated with low adherence rates. MATERIALS AND METHODS: Women 45-65 years of age were interviewed by questionnaire containing 15 structured questions focused on socioeconomic status and barriers to screening. RESULTS: A total of 3,313 women completed the questionnaire. The main reasons for avoiding screening were work absenteeism (18.9%), fear of painful examination (18.39%), and poor understanding of mammography screening (14.94%). CONCLUSION: Education is required to increase awareness among women about the utility and availability of breast screening services. This report provides information on the appropriate level of intervention needed to increase screening participation in Hungary and other developing countries in Central Eastern Europe to reduce breast cancer-related mortality.

[Second breast conserving surgery and interstitial radiotherapy for the treatment of breast tumor local recurrences. Five-year results]. / Második emlomegtartó mutét és szövetközi sugárkezelés az emlodaganat lokális kiújulásának kezelésére. Ötéves eredmények.

INTRODUCTION AND AIM: To report the clinical outcomes of second breast-conserving therapy with perioperative interstitial radiotherapy for the treatment of ipsilateral breast tumor recurrences. METHOD: Between 1999 and 2015, 33 patients, presenting with an ipsilateral breast tumor recurrence after previous breast conserving therapy, were salvaged by re-excision and perioperative high-dose-rate interstitial brachytherapy. A median of 8 (range: 4-24) catheters were implanted into the tumor bed intraoperatively. A total dose of 22 Gy in 5 fractions of 4.4 Gy was delivered to the tumor bed with a margin of 1-2 cm, on 3 consecutive days. The adjuvant systemic treatments consisted of hormonal therapy for 24 patients (73%) and chemotherapy for 6 patients (18%). The survival results were estimated by the Kaplan-Meier method. Late side effects and cosmetic results were also registered. RESULTS: The median follow-up time following the second breast conserving therapy was 61 months (range: 26-189 months). During the follow-up, 4 patients (12.1%) developed second local recurrence. The five-year actuarial rates of the second local, regional and distant recurrence were 6.3%, 6.1%, and 14.9%, respectively. The five-year probabilities of disease-free, cancer-specific and overall survival were 76.2%, 92.4%, and 89.2%, respectively. Four (12%), 19 (58%), 4 (12%) and 6 (18%) patients had excellent, good, fair and poor cosmetic results, respectively. Grade 2 and 3 fibrosis developed in 9 (27%) and 1 (3%) patients. Asymptomatic fat necrosis was detected in 7 (21%) women. CONCLUSION: Second breast conserving therapy with perioperative high-dose-rate interstitial brachytherapy is a safe and feasible option for the management of ipsilateral breast tumor recurrences. Interstitial brachytherapy may decrease the risk of second local relapse with acceptable cosmetic results and low rate of late side effects. Hence, in selected cases it can provide a feasible alternative to salvage mastectomy. Orv Hetil. 2018; 159(11): 430-438.

[Evaluation of clinicopathological findings and cosmetic outcome of 100 immediate postmastectomy breast reconstruction cases]. / Azonnali, postmastectomiás emlorekonstrukciókkal szerzett tapasztalatok. Száz eset klinikopatológiai utánkövetése és a kozmetikai eredmények felmérése.

INTRODUCTION: Immediate breast reconstruction provides oncological safety, requires longer operation time. It does not influence the initiation of adjuvant therapy and radiological control, and results in favourable cosmetic outcome. AIM: Assessing the Hungarian data of immediate postmastectomy breast reconstructions, and comparing them to international findings. METHOD: Between May, 2011 and September, 2014 121 therapeutic and prophylactic, postmastectomy immediate breast reconstructions were performed in 100 patients. The clinico-pathological findings were assessed retrospectively, and surgical, oncological and cosmetic outcomes were evaluated statistically. RESULTS: The mean age of patients was 42.6 years, the follow up time was 29.4 months, and the duration of operation was 132 minutes. Skin-sparing mastectomy was performed most commonly (64%) with submuscular tissue expander placement (70%). Early postoperative complication was identified in 18 patients, and loco-regional recurrence in 1 patient. Most patients (89%) were satisfied with the cosmetic outcome. The average initiation time of adjuvant therapy was 4.8 weeks. CONCLUSIONS: Immediate breast reconstruction is a safe and effective option in line with international findings. Orv. Hetil., 2016, 157(46), 1830-1838.

[Breast cancer care quality analysis of the National Institute of Oncology in Hungary according to the requirements of European Society of Breast Cancer Specialists (EUSOMA)]. / A European Society of Breast Cancer Specialists (EUSOMA) eloírásainak megfelelo emlorákellátás minoségbiztosítási elemzése az Országos Onkológiai Intézetben.

INTRODUCTION: The European Society of Breast Cancer Specialists has created quality indicators for breast units to establish minimum standards and to ensure specialist multimodality care with the conscious aim of improving outcomes and decreasing breast cancer mortality. AIM: The aim of this study was to analyse the breast cancer care in the National Institute of Oncology according to the European Society of Breast Cancer Specialists requirements and in a large number of cases in order to present representative clinico-pathological data on the incidence of breast cancer in Hungary. METHOD: According to the European Society of Breast Cancer Specialists uniformed criteria clinico-pathological data of multimodality treated breast cancer cases were retrospectively analysed between June 1, 2011 and May 31, 2012. RESULTS: During the period of interest 906 patients underwent breast surgery for malignant or benign lesions. According to the European Society of Breast Cancer Specialists quality indicators the breast cancer care of the National Institute of Oncology is eligible. CONCLUSIONS: The diagnostic modalities and multimodality care of breast cancer of the National Institute of Oncology breast unit meets the critical mass and minimum standards of the European Society of Breast Cancer Specialists criteria. Orv. Hetil., 2016, 157(42), 1674-1682.

Evaluation of patient knowledge, desire, and psychosocial background regarding postmastectomy breast reconstruction in Hungary: a questionnaire study of 500 cases.

BACKGROUND: According to European guidelines, breast cancer patients requiring mastectomy should be informed about available options regarding breast reconstruction. There are clear differences in the quality standards of oncoplastic care throughout Europe, with slight improvements in Central European countries like Hungary. The aim of the present investigation was to evaluate patients' knowledge and demand for postmastectomy breast reconstruction, as well as their psychosocial background regarding decision-making. MATERIAL AND METHODS: A questionnaire containing 15 structured questions was given to 500 breast cancer patients on the day before undergoing mastectomy. The questions focused on the emotional impact of the malignant disease and the loss of a breast; the importance of environmental conditions; the desire for breast reconstruction; and patients' knowledge and sources of information about the procedure. All answers were statistically analyzed in the context of patient age, marital status, educational level, and place of residence. RESULTS: Descriptive statistical results of the answers to all questions, as well as associations of the different aspects of the decision-making process, are presented. CONCLUSIONS: Hungarian breast cancer patients have very limited knowledge regarding breast reconstruction. We confirmed that patients scheduled for mastectomy have a great degree of anxiety due to their disease and breast loss. Almost 50% of the responders declared their desire for postmastectomy breast reconstruction. Patient's age, residence, educational level, marital status, and profession were confirmed as predictive factors in the decision-making process for breast reconstruction.

[Sentinel lymph node biopsy after neoadjuvant chemotherapy in breast cancer]. / Orszemnyirokcsomó-biopszia neoadjuváns kemoterápiát igénylõ emlõrákoknál.

The indication of neoadjuvant chemotherapy has been recently extended; it is now applied not only in locally advanced breast cancer but in primarily resecable tumours as well, in order to promote breast conservation. Based on recent clinical results, the reconsideration of traditional lymph node dissection in axillary staging is timely in patients receiving neoadjuvant chemotherapy. Precise axillary staging needs surgical removal of lymph nodes. Based on prospective randomised trials, sentinel lymph node biopsy appears to be appropriate for axillary staging even in tumours requiring neoadjuvant treatment. The extended indication of sentinel lymph node biopsy raises several questions and problems. In the present paper the authors review the results and possible limitations of sentinel lymph node biopsy in relation to neoadjuvant chemotherapy.