ESO-ESMO fifth international consensus guidelines for breast cancer in young women (BCY5).

We dedicate this manuscript in memory of a dear friend and colleague Bella Kaufman. The fifth International Consensus Symposium for Breast Cancer in Young Women (BCY5) took place virtually in October 2020, organized by the European School of Oncology (ESO) and the European Society of Medical Oncology (ESMO). Consensus recommendations for the management of breast cancer in young women were updated from BCY4 with incorporation of new evidence to inform the guidelines. Areas of research priorities as well as specificities in different geographic and minority populations were identified. This manuscript summarizes the ESO-ESMO international consensus recommendations, which are also endorsed by the European Society of Breast Specialists (EUSOMA).

Axillary staging for breast cancer during pregnancy: feasibility and safety of sentinel lymph node biopsy.

BACKGROUND: Safety of sentinel lymph node (SLN) biopsy for breast cancer during pregnancy is insufficiently explored. We investigated efficacy and local recurrence rate in a large series of pregnant patients. PATIENTS AND METHODS: Women diagnosed with breast cancer who underwent SLN biopsy during pregnancy were identified from the International Network on Cancer, Infertility and Pregnancy, the German Breast Group, and the Cancer and Pregnancy Registry. Chart review was performed to record technique and outcome of SLN biopsy, locoregional and distant recurrence, and survival. RESULTS: We identified 145 women with clinically N0 disease who underwent SLN during pregnancy. The SLN detection techniques were as follows: 99mTc-labeled albumin nanocolloid only (n = 96; 66.2%), blue dye only (n = 14; 9.7%), combined technique (n = 15; 10.3%), or unknown (n = 20; 13.8%). Mapping was unsuccessful in one patient (0.7%) and she underwent an axillary lymph node dissection (ALND). Mean number of SLNs was 3.2 (interquartile range 1-3; missing n = 15). Positive SLNs were found in 43 (29.7%) patients and 34 subsequently underwent ALND. After a median follow-up of 48 months (range 1-177), 123 (84.8%) patients were alive and free of disease. Eleven patients experienced a locoregional relapse, including 1 isolated ipsilateral axillary recurrence (0.7%). Eleven (7.6%) patients developed distant metastases, of whom 9 (6.2%) died of breast cancer. No neonatal adverse events related to SLN procedure during pregnancy were reported. CONCLUSIONS: SLN biopsy during pregnancy has a comparably low axillary recurrence rate as in nonpregnant women. Therefore, this method can be considered during pregnancy instead of standard ALND for early-stage, clinically node-negative breast cancer.

Improved prognosis of young patients with breast cancer undergoing breast-conserving surgery.

BACKGROUND: The aim of the present study was to evaluate how breast cancer prognosis has evolved over time in young women treated with breast-conserving surgery (BCS). METHODS: Data from patients younger than 40 years who had BCS and whole-breast radiotherapy in a single cancer centre between 1997 and 2010 were analysed. The patients were followed until 2016. Endpoints were local recurrence, any breast cancer-related event and death from any cause. RESULTS: A total of 1331 patients were included in the study. After a median follow-up of 9·3 years, 114 local recurrences, 289 breast cancer-related events and 138 deaths had occurred. Women were divided into three groups of similar size based on tertiles of the date of diagnosis: 1997-2002 (524 patients), 2003-2005 (350) and 2006-2010 (457). The risk of local recurrence was 1·42 per 100 person-years in women diagnosed in the first interval, 0·85 per 100 person-years in the second and 0·48 per 100 person-years in the third (P for trend = 0·028). The respective values were 3·01, 2·52 and 2·07 per 100 person-years for any breast cancer-related event (P = 0·004), and 1·59, 1·22 and 0·64 per 100 person-years for death (P = 0·003). Each passing year was associated with a decreasing risk of local recurrence (hazard ratio (HR) 0·93, 95 per cent c.i. 0·87 to 1·00), any breast cancer-related event (HR 0·94, 0·91 to 0·98) and death (HR 0·89, 0·83 to 0·94). A major improvement in prognosis was observed after 2005, when the classification of breast cancer molecular subtypes and use of trastuzumab were implemented in routine clinical practice. CONCLUSION: In the past two decades, both local control and overall prognosis have improved significantly in young women (aged less than 40 years) with breast cancer who undergo BCS.

Contralateral risk reducing mastectomy in patients with sporadic breast cancer. Benefits and hazards.

During the last years an improving outcome of breast conserving surgery was observed along with the availability of diagnostic procedures allowing early diagnosis. Nevertheless, women with breast cancer are more frequently requesting a radical approach comprising contralateral mastectomy even if they do not have a demonstrated increased genetic risk. In this paper we reviewed the main reasons patients ask for aggressive preventive surgery, the perceived and the real risks of developing contralateral breast cancer, and the potential, if any, survival benefits along with the hazards associated to contralateral risk reducing mastectomy. A respectful management should be given to these women within a multi-disciplinary team. Psychological support is highly encouraged cope fears and uncertainties but treating physicians should provide patients with comprehensive and unbiased data to take the best decision for the single person. Physicians should also give clear information on the benefits of adjuvant therapies which are reducing the incidence of contralateral breast cancer and also of the possible influences of healthy lifestyle (weight control, physical activity, diet) as effective preventive methods.

Physical function of the upper limb after breast cancer surgery. Results from the SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial.

BACKGROUND: The SOUND (Sentinel node vs. Observation after axillary Ultra-souND) trial is an ongoing prospective randomized study comparing sentinel node biopsy vs. no axillary surgical staging in patients with small breast cancer and negative pre-operative ultra-sound of the axilla. PATIENTS AND METHODS: The first 180 recruited patients were administered the QuickDASH (Disability Arm and Shoulder) questionnaire at different time points (before surgery, 1 week, 6 months and 1 year after surgery) to evaluate the physical function of the ipsilateral upper limb, The QuickDASH score ranges from 0 (no disability) to 100 (complete disability). RESULTS: 176 patients were available for analysis (94 in SNB arm and 82 in observation arm). The two groups were comparable with respect to age, tumor characteristics and treatments. Pre-surgery score values were 3.0% and 2.7% in the SNB arm and observation arm, respectively (P = 0.730). One week after surgery, the score increased to 24.0% in the SNB arm and 10.6% in the observation arm (P < 0.001). After 6 and 12 months, the score decreased in both arms to values similar to baseline values. The overall trend in time of the score was significantly different between the two arms (P < 0.001), even after the exclusion of five patients who received AD in the SNB arm (P < 0.001). CONCLUSIONS: Patients who underwent SNB had a significantly higher rate of disability in the early post-operative period compared to patients who did not. The avoidance of SNB might translate into a considerable reduction of physical and emotional distress.

Second Axillary Sentinel Lymph Node Biopsy for Breast Tumor Recurrence: Experience of the European Institute of Oncology.

PURPOSE: This retrospective study aimed to determine the feasibility, accuracy, and recurrence rates of lymphoscintigraphy and the new sentinel lymph node biopsy (SLNB) for patients with ipsilateral breast tumor recurrences who were treated previously with conservative surgery and had negative SLNB results. METHODS: The study was conducted at the European Institute of Oncology in Milan and included 212 patients with the diagnosis of operable local breast cancer recurrence. They had been treated previously with conservative surgery and showed negative SLNB results. They subsequently underwent additional breast surgery and a second SLNB between May 2001 and December 2011. RESULTS: Preoperative lymphoscintigraphy demonstrated at least one new axillary sentinel lymph node (SLN) in 207 patients (97.7 %), whereas no drainage was observed in five patients (2.3 %). One or more SLNs were surgically removed from 196 of the 207 patients. Isolation of SLNs from the remaining 11 patients could not be accomplished. The success rate for the SLNB was 92.5 %. Extra-axillary drainage pathways were visualized in 17 patients (8 %). The annual axillary recurrence rate after a median follow-up period of 48 months was 0.8 %, and the cumulative incidence of axillary recurrence at 5 years was 3.9 %. CONCLUSIONS: A second SLNB should be considered for patients with operable local breast tumor recurrence who underwent conservative surgery and had negative SLNB results. The procedure is technically feasible and accurate for selected patients.

Long-term follow-up of 5262 breast cancer patients with negative sentinel node and no axillary dissection confirms low rate of axillary disease.

AIM: It is established that axillary dissection (AD) can be safely avoided in breast cancer patients with a negative sentinel node (SN). In the present study we assessed whether the rate of axillary disease was sufficiently low on long term follow-up to consolidate the policy of AD avoidance. METHODS: We retrospectively analysed data on 5262 consecutive primary breast cancer patients with clinically negative axilla and negative SN, treated from 1996 to 2006, who did not receive AD. We used univariate and multivariate analyses to assess the influence of patient and tumour characteristics on first events and survival. The primary endpoint was the development of axillary disease as first event. RESULTS: After a median follow-up of 7.0 years (interquartile range 5.4-8.9 years) survival for the series was high (91.3%; 95% CI 90.3-92.3 at 10 years) and only 91 (1.7%) patients developed axillary disease as first event. Axillary disease was significantly more frequent in patients with the following characteristics: <35 years at diagnosis, tumour >1 cm, multifocality/multicentricity, G3, ductal histotype, Ki67 ≥ 30%, peritumoral vascular invasion, luminal B-like subtype, HER2 positivity, mastectomy, and not receiving radiotherapy. CONCLUSION: Long-term follow-up of our large series confirms that axillary metastasis is infrequent when AD is omitted in SN-negative breast cancer patients, and has low impact on overall survival.

The indocyanine green method is equivalent to the 99mTc-labeled radiotracer method for identifying the sentinel node in breast cancer: a concordance and validation study.

AIMS: The aim of this study was to assess concordance between the indocyanine green (ICG) method and (99m)Tc-radiotracer method to identify the sentinel node (SN) in breast cancer. Evidence supports the feasibility and efficacy of the ICG to identify the SN, however this method has not been prospectively compared with the gold-standard radiotracer method in terms of SN detection rate. METHODS: Between June 2011 and January 2013, 134 women with clinically node-negative early breast cancer received subdermal/peritumoral injection of (99m)Tc-labeled tracer for lymphoscintigraphy, followed by intraoperative injection of ICG for fluorescence detection of SNs using an exciting light source combined with a camera. In all patients, SNs were first identified by the fluorescence method (ICG-positive) and removed. A gamma ray-detecting probe was then used to determine whether ICG-positive SNs were hot ((99m)Tc-positive) and to identify and remove any (99m)Tc-positive (ICG-negative) SNs remaining in the axilla. The study was powered to perform an equivalence analysis. RESULTS: The 134 patients provided 246 SNs, detected by one or both methods. 1, 2 and 3 SNs, respectively, were detected, removed and examined in 70 (52.2%), 39 (29.1%) and 17 (12.7%) patients; 4-10 SNs were detected and examined in the remaining 8 patients. The two methods were concordant for 230/246 (93.5%) SNs and discordant for 16 (6.5%) SNs. The ICG method detected 99.6% of all SNs. CONCLUSIONS: Fluorescent lymphangiography with ICG allows easy identification of axillary SNs, at a frequency not inferior to that of radiotracer, and can be used alone to reliably identify SNs.

The effect of metformin on apoptosis in a breast cancer presurgical trial.

BACKGROUND: Metformin has been associated with antitumour activity in breast cancer (BC) but its mechanism remains unclear. We determined whether metformin induced a modulation of apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) overall and by insulin resistance status in a presurgical trial. METHODS: Apoptosis was analysed in core biopsies and in surgical samples from 100 non-diabetic BC patients participating in a randomised trial of metformin vs placebo given for 4 weeks before surgery. RESULTS: Eighty-seven subjects (45 on metformin and 42 on placebo) were assessable for TUNEL measurement at both time points. TUNEL levels at surgery were higher than that at baseline core biopsy (P<0.0001), although no difference between arms was noted (metformin arm: median difference surgery-biopsy levels +4%, interquartile range (IQR): 2-12; placebo arm: +2%, IQR: 0-8, P=0.2). Ki67 labelling index and TUNEL levels were directly correlated both at baseline and surgery (Spearman's r=0.51, P<0.0001). In the 59 women without insulin resistance (HOMA index<2.8) ,there was a higher level of TUNEL at surgery on metformin vs placebo (median difference on metformin +4%, IQR: 2-14 vs +2%, IQR: 0-7 on placebo), whereas an opposite trend was found in the 28 women with insulin resistance (median difference on metformin +2%, IQR: 0-6, vs +5%, IQR: 0-15 on placebo, P-interaction=0.1). CONCLUSION: Overall, we found no significant modulation of apoptosis by metformin, although there was a trend to a different effect according to insulin resistance status, with a pattern resembling Ki67 changes. Apoptosis was significantly higher in the surgical specimens compared with baseline biopsy and was directly correlated with Ki67. Our findings provide additional evidence for a dual effect of metformin on BC growth according to insulin resistance status.

Mastectomy without radiotherapy: outcome analysis after 10 years of follow-up in a single institution.

The aim of this study was to identify the prognostic factors associated with the risk of loco-regional recurrence (LRR) of women undergoing mastectomy and complete axillary dissection without radiotherapy. We analyzed data from 650 women operated between 1997 and 2001 in a single institution. Median follow-up was 10 years. Overall survival was 89.8 % at 5 years and 76.6 % at 10 years. The 10-year cumulative incidence of LRRs was 10.0 % (5.0, 10.5, 15.8, and 18.5 % in patients with 0, 1-3, 4-9, and ≥10 positive lymph nodes (LNs), respectively). Sixty-two (9.5 %) LRRs were observed, 5 (0.8 %) of which occurred in the axillary LNs. Supraclavicular LNs recurrences (n = 16, 2.5 %) occurred more frequently in patients with four or more positive LNs, Ki-67 ≥ 20 % or extensive peritumoral vascular invasion (PVI). At multivariable analysis, nodal status was the only prognostic factor for local events, while nodal status, Ki-67 and PVI were significant prognostic factors for recurrences in the regional LNs. Moreover, within each category of positive LNs, high values of Ki-67 and extensive PVI were associated with the highest risk of LRR while low values of Ki-67 and absence of extensive PVI were associated with the lowest risk of LRR. Women with node-negative tumors have the lowest risk of LRR and represent the group of patients that might benefit the least from radiotherapy. PVI and Ki-67 might help tailoring PMRT indications among patients with positive LNs. Finally, the very low incidence of recurrences in the axillary LNs raises questions about the inclusion of the axilla in the radiation field.

Prognosis in women with small (T1mic,T1a,T1b) node-negative operable breast cancer by immunohistochemically selected subtypes.

Knowledge is limited about prognostic significance of breast cancer subtypes among women with small invasive node-negative breast tumours. We explored patterns of recurrence in 1691 women with pT1mic/T1a/T1b, pN0 and M0 breast cancer according to four immunohistochemically defined tumour subtypes: (i) Luminal A (ER-positive, PgR-positive, HER2-negative and Ki-67 < 14%); (ii) Luminal B (ER-positive and/or PgR-positive, HER2-positive and/or Ki-67 ≥ 14%); (iii) HER2-positive, both endocrine receptors absent; and (iv) Triple Negative. At multivariate analysis, women with the Triple Negative breast cancer subtype had an increased risk of loco-regional relapse (LRR) (Hazards Ratio (HR) 3.58; 95%CI: 1.40-9.13) and breast cancer related events (HR 2.18; 95%CI: 1.04-4.57). Overall, Luminal B subtype was not associated with a statistically significant increased risk of recurrence compared with Luminal A, while patients with Luminal B subtype tumours overexpressing HER2 had a 2 fold risk of reduced breast cancer related survival (BCS), but not an increased risk of LRR and distant metastases. Women with HER2 breast cancer subtype had a statistically significant increased risk of LRR (HR 4.53; 95%CI: 1.56-13.1), distant metastases and reduced BCS (HR 3.22; 95%CI: 1.44-7.18) and overall survival (HR 2.87; 95%CI: 1.05-7.89) when compared with the Luminal A subtype, at multivariate analysis. In conclusion, women with small size, node-negative, breast cancer are at higher risk of relapse if with HER2-positive endocrine receptor absent or Triple Negative disease.

Managing pregnant women with cancer: personal considerations and a review of the literature.

Managing cancer during pregnancy is a very critical clinical situation. It is relatively rare but once encountered, it poses several clinical and sometimes social and ethical conflicts as well. Generalizing treatment decisions is very hard and in our opinion, each case should be discussed in a multidisciplinary manner acknowledging patients' opinion as well to reach a proper decision. In this review we touch on the available evidence on managing cancer patients diagnosed during the course of pregnancy in an attempt to provide some guidance for clinicians dealing with such cases.

Quality indicators in breast cancer care.

To define a set of quality indicators that should be routinely measured and evaluated to confirm that the clinical outcome reaches the requested standards, Eusoma has organised a workshop during which twenty four experts from different disciplines have reviewed the international literature and selected the main process and outcome indicators available for quality assurance of breast cancer care. A review of the literature for evidence-based recommendations have been performed by the steering committee. The experts have identified the quality indicators also taking into account the usability and feasibility. For each of them it has been reported: definition, minimum and target standard, motivation for selection and level of evidence (graded according to AHRO). In overall 17 main quality indicators have been identified, respectively, 7 on diagnosis, 4 on surgery and loco-regional treatment, 2 on systemic treatment and 4 on staging, counselling, follow-up and rehabilitation. Breast Units in Europe are invited to comply with these indicators and monitor them during their periodic audit meetings.

Prognosis and adjuvant treatment effects in selected breast cancer subtypes of very young women (<35 years) with operable breast cancer.

BACKGROUND: There is limited knowledge about prognosis of selected breast cancer subtypes among very young women. PATIENTS AND METHODS: We explored patterns of recurrence by age according to four immunohistochemically defined tumor subtypes: Luminal A and Luminal B (estrogen receptor positive and/or progesterone receptor positive and either human epidermal growth factor receptor 2 (HER2) positive and/or high Ki-67), HER2-positive (and) endocrine receptor absent and Triple Negative, in 2970 premenopausal patients with pT1-3, pN0-3 and M0 breast cancer. RESULTS: Patients <35 years of age (315, 11%) presented a significantly increased risk of recurrence and death [hazards ratio (HR) = 1.65, 95% confidence interval (CI) 1.30-2.10 and HR = 1.78, 95% CI 1.12-2.85, respectively] when compared with older patients (2655, 89%) with similar characteristics of disease. This was true considering patients with Luminal B [HR = 1.62, 95% CI 1.21-2.18 for disease-free survival (DFS) and HR = 2.09, 95% CI 0.96-4.53 for overall survival (OS)] and with Triple Negative (HR = 2.04, 95% CI 1.11-3.72 for DFS and HR = 2.20, 95% CI 1.10-4.41 for OS) breast cancer, observing the highest risk of recurrence in the younger patients with HER2-positive breast cancer (HR = 2.37, 95% CI 1.12-5.02) when compared with older patients. CONCLUSIONS: Very young patients with Triple Negative, Luminal B or HER2-positive breast cancer have a worse prognosis when compared with older patients with similar characteristics of disease.

Analysis of local and regional recurrences in breast cancer after conservative surgery.

BACKGROUND: A minority of patients treated conservatively for breast cancer will develop local or regional recurrences. Our aim was to determine how their occurrence may be linked to the evolution of the disease. PATIENTS AND METHODS: We analyzed 2784 women treated for early-stage breast cancer by quadrantectomy and whole-breast irradiation in a single institution. We evaluated the prognostic factors associated with local, regional and distant recurrences and the prognostic value of local and regional recurrences on systemic progression. RESULTS: After a median follow-up of 72 months, we observed 33 local events, 35 regional events and 222 metastases or deaths as first events (5-year cumulative incidence 1.1%, 1.2% and 7.6%, respectively). Size, estrogen receptor status, Her2/Neu and Ki-67 were associated with all three types of events, while axillary status and vascular invasion were associated only with the occurrence of metastases or death. Young age increased the risk of local recurrence. Local and regional recurrences were associated with an increased risk of systemic progression: hazard ratios 2.5 [95% confidence interval (CI) 1.1-5.8] and 5.3 (95% CI 3.0-9.5), respectively. CONCLUSIONS: Local and regional recurrences after breast-conserving surgery are rare events. They are markers of tumor aggressiveness and indicators of an increased likelihood of distant metastases.

Unavoidable mastectomy for ipsilateral breast tumour recurrence after conservative surgery: patient outcome.

BACKGROUND: In the case of ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS), a second conservative surgical approach maybe considered in some motivated patients whereas in others mastectomy is unavoidable. PATIENTS AND METHODS: From 1997 to 2004, 282 patients presented at the European Institute of Oncology with an operable invasive IBTR after BCS. One hundred and sixty-one (57%) underwent a second conservative surgery, whereas 121 patients (43%) were given a mastectomy and represent the study population. We investigated the prognosis and determined predictive factors of outcome. RESULTS: Median time from primary breast cancer to IBTR was 41 months (range 5-213). Recurrences were T2-T4 and/or multifocal in 83 cases (68.6%). With a median follow-up of 5 years after mastectomy, 5-year overall survival (OS) and disease-free survival (DFS) were 73.3% [95% confidence interval (CI) 65.0% to 81.6%] and 50.4% (95% CI 40.9% to 59.8%), respectively. At the multivariate analysis, early onset of IBTR, presence of vascular invasion and Ki67 >or=20 of the recurrent tumour were found to significantly affect both DFS and OS. CONCLUSIONS: In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors.

Oncological results of immediate breast reconstruction: long term follow-up of a large series at a single institution.

BACKGROUND: Reconstruction of the breast after mastectomy is an integral part of the complete management of breast cancer. However, a delay in the reconstruction is usually proposed after the mastectomy in case of invasive cancer, while there is a general agreement for immediate breast reconstruction in case of in situ tumors. PATIENTS AND METHODS: Among a total of 677 patients having undergone a mastectomy between 1997 and 2001, 518 (76.5%) underwent an immediate breast reconstruction (IBR). All the patients had a Patey mastectomy for invasive cancer (T1-T3). An adjuvant medical treatment was given according to the biological characteristics of the tumor and lymph node status. No patient received any kind of radiotherapy. The median follow up was 70 months (range 13-114). RESULTS: The local recurrence rate was 5.2% for the group of IBR and 9.4% for the mastectomy group without IBR (NoIBR). The regional metastases rate was 1.4 vs. 1.3%. The rate of distant metastases was 13.9 vs. 16.4%. Contra-lateral breast tumor was observed in 1.5 vs. 1.3%. Death rate was 10.4 vs. 16.4%. No statistical difference was observed between the two groups in terme of overall survival (OS) and disease free survival (DFS) (HR(IBR vs. NoIBR): 1.03 and 0.99 for OS and DFS, respectively). CONCLUSION: At our institution we have compared a large series that have undergone IBR (518) with a control group (159) and followed over a prolonged period of time (70 months). This study provides the best available results to suggest that IBR is a safe and reliable treatment option for the managing invasive breast cancer.

[Conservative approach for breast cancer. The experience of the European Institute of Oncology]. / L'approccio conservativo al carcinoma mammario.L'esperienza dell'Istituto Europeo di Oncologia.

Conservative surgery represents the standard care for patients with early breast cancer. The aim of this review was to discuss the extension of conservative surgery in controversial fields such as after primary chemotherapy for large tumours or the possibility to repeat conservative surgery for a local reappearance. The project of a conservative approach to breast cancers continues with sentinel node biopsy which is worldwide performed more and more frequently. In our institute sentinel node biopsy is the standard procedure in the axillary staging of breast cancer even in those clinical scenarios which were previously considered either controversial or a contraindication such as in multicentric breast cancer, during pregnancy, in intra-ductal neoplasias, after primary chemotherapy, and male breast cancer. This conservative approach is completed by the possibility to deliver a partial breast irradiation and to provide patients with more personalized adjuvant treatments tailored on the biological features of the tumour.

Is avoiding post-mastectomy radiotherapy justified for patients with four or more involved axillary nodes and endocrine-responsive tumours? Lessons from a series in a single institution.

BACKGROUND: Current guidelines for post-mastectomy radiotherapy (PMRT) derive largely from extrapolating information from multicentre trials. The aim of this study was to describe outcomes of patients who underwent mastectomy without radiotherapy in a single institution. PATIENTS AND METHODS: 650 patients had total mastectomy and axillary dissection without PMRT between 1997 and 2001. Median follow-up was 65 months. RESULTS: 5-year cumulative incidence of loco-regional recurrence (LRR) was 6.8% (3.0, 8.1, 9.9% in node negative, 1-3, > or =4 positive nodes, respectively). At the multivariate analysis, positive lymph nodes and endocrine non-responsive tumours were found to shorten LRR disease-free survival. In patients with positive hormone receptors, 5-year cumulative incidence of LRR disease-free survival were 2.3%, 7.6% and 7.6% for node negative, 1-3 and > or =4 positive lymph nodes, respectively. The same figures were 5.9%, 10.3% and 20.0% in patients with endocrine non-responsive tumours. CONCLUSIONS: patients with endocrine-responsive tumours treated by mastectomy and complete (level III) axillary dissection have a low risk of LRR even if four or more positive lymph nodes are involved, thus giving rise to doubts on the use of PMRT in this subset of patients. On the other hand, PMRT might play a role for patients with negative hormone receptors and four or more positive nodes.