Long-term prognosis in breast cancer is associated with residual disease after neoadjuvant systemic therapy but not with initial nodal status.

BACKGROUND: This follow-up analysis of a Swedish prospective multicentre trial had the primary aim to determine invasive disease-free (IDFS), breast cancer-specific (BCSS) and overall survival (OS) rates, and their association with axillary staging results before and after neoadjuvant systemic therapy for breast cancer. METHODS: Women who underwent neoadjuvant systemic therapy for clinically node-positive (cN+) or -negative (cN0) primary breast cancer between 2010 and 2015 were included. Patients had a sentinel lymph node biopsy before and/or after neoadjuvant systemic therapy, and all underwent completion axillary lymph node dissection. Follow-up was until February 2019. The main outcome measures were IDFS, BCSS and OS. Univariable and multivariable Cox regression analyses were used to identify independent factors associated with survival. RESULTS: The study included a total of 417 women. Median follow-up was 48 (range 7-114) months. Nodal status after neoadjuvant systemic therapy, but not before, was significantly associated with crude survival: residual nodal disease (ypN+) resulted in a significantly shorter 5-year OS compared with a complete nodal response (ypN0) (83·3 versus 91·0 per cent; P = 0·017). The agreement between breast (ypT) and nodal (ypN) status after neoadjuvant systemic therapy was high, and more so in patients with cN0 tumours (64 of 66, 97 per cent) than those with cN+ disease (49 of 60, 82 per cent) (P = 0·005). In multivariable analysis, ypN0 (hazard ratio 0·41, 95 per cent c.i. 0·22 to 0·74; P = 0·003) and local radiotherapy (hazard ratio 0·23, 0·08 to 0·64; P = 0·005) were associated with improved IDFS, and triple-negative molecular subtype with worse IDFS. CONCLUSION: The present findings underline the prognostic significance of nodal status after neoadjuvant systemic therapy. This confirms the clinical value of surgical axillary staging after neoadjuvant systemic therapy.

Omitting completion axillary lymph node dissection after detection of sentinel node micrometastases in breast cancer: first results from the prospective SENOMIC trial.

BACKGROUND: Completion axillary lymph node dissection has been abandoned widely among patients with breast cancer and sentinel lymph node micrometastases, based on evidence from prospective RCTs. Inclusion in these trials has been subject to selection bias, with patients undergoing mastectomy being under-represented. The aim of the SENOMIC (omission of axillary lymph node dissection in SENtinel NOde MICrometases) trial was to confirm the safety of omission of axillary lymph node dissection in patients with breast cancer and sentinel lymph node micrometastases, and including patients undergoing mastectomy. METHODS: The prospective SENOMIC multicentre cohort trial enrolled patients with breast cancer and sentinel lymph node micrometastases who had breast-conserving surgery or mastectomy at one of 23 Swedish hospitals between October 2013 and March 2017. No completion axillary lymph node dissection was performed. The primary endpoint was event-free survival, with a trial accrual target of 452 patients. Survival proportions were based on Kaplan-Meier survival estimates. RESULTS: The trial included 566 patients. Median follow-up was 38 (range 7-67) months. The 3-year event-free survival rate was 96.2 per cent, based on 26 reported breast cancer recurrences, including five isolated axillary recurrences. The unadjusted 3-year event-free survival rate was higher than anticipated, but differed between patients who had mastectomy and those who underwent breast-conserving surgery (93.8 versus 97.8 per cent respectively; P = 0.011). Patients who underwent mastectomy had significantly worse tumour characteristics. On univariable Cox proportional hazards regression analysis, patients who had mastectomy without adjuvant radiotherapy had a significantly higher risk of recurrence than those who underwent breast-conserving surgery (hazard ratio 2.91, 95 per cent c.i. 1.25 to 6.75). CONCLUSION: After 3 years, event-free survival was excellent in patients with breast cancer and sentinel node micrometastases despite omission of axillary lymph node dissection. Long-term follow-up and continued enrolment of patients having mastectomy, especially those not receiving adjuvant radiotherapy, are of utmost importance.

Carbon tattooing for targeted lymph node biopsy after primary systemic therapy in breast cancer: prospective multicentre TATTOO trial.

BACKGROUND: Several techniques for targeted lymph node biopsy in patients with node-positive breast cancer receiving primary systemic therapy are in use, each with their inherent advantages and disadvantages. The aim of the TATTOO trial was to evaluate the feasibility and accuracy of carbon tattooing of positive lymph nodes as a method for targeted lymph node biopsy avoiding radiation exposure, high costs, and preoperative localization procedures. METHODS: Patients with initially cT1-4c cN1-3 cM0 invasive breast cancer were included in this prospective multicentre trial. Before initiation of primary systemic therapy, a carbon suspension was injected into the most suspicious axillary lymph node. Targeted lymph node biopsy was performed in all patients after completion of primary systemic therapy. Additional sentinel lymph node biopsy was done in those with axillary downstaging, and completion axillary lymph node dissection in patients still presenting with suspicious lymph nodes. RESULTS: A total of 118 patients were included and 110 were eligible for data analysis. The detection rate for the targeted lymph node was 93.6 per cent (103 of 110), and the sentinel lymph node was identical to the targeted lymph node in 60 per cent. The false-negative rate for the combination of targeted and sentinel node lymph node biopsy (targeted axillary dissection) was 9 per cent. CONCLUSION: Targeted axillary dissection after carbon tattooing is associated with a high detection rate, an acceptable false-negative rate, and appears feasible for clinical use even in healthcare settings with limited resources.

Do clinical trials truly mirror their target population? An external validity analysis of national register versus trial data from the Swedish prospective SENOMIC trial on sentinel node micrometastases in breast cancer.

PURPOSE: Increasing evidence suggests that completion axillary lymph node dissection (ALND) may be omitted in breast cancer patients with limited axillary nodal metastases. However, the representativeness of trial participants for the original clinical practice population, and thus, the generalizability of published trials have been questioned. We propose the use of background data from national registers as a means to assess whether trial participants mirror their target population and to strengthen the generalizability and implementation of trial outcomes. METHODS: The Swedish prospective SENOMIC trial, omitting a completion ALND in breast cancer patients with sentinel lymph node micrometastases, reached full target accrual in 2017. To assess the generalizability of trial results for the target population, a comparative analysis of trial participants versus cases reported to the Swedish National Breast Cancer Register (NKBC) was performed. RESULTS: Comparing 548 trial participants and 1070 NKBC cases, there were no significant differences in age, tumor characteristics, breast surgery, or adjuvant treatment. Only the mean number of sentinel lymph nodes with micrometastasis per individual was lower in trial participants than in register cases (1.06 vs. 1.09, p = 0.037). CONCLUSIONS: Patients included in the SENOMIC trial are acceptably representative of the Swedish breast cancer target population. There were some minor divergences between trial participants and the NKBC population, but taking these into consideration, upcoming trial outcomes should be generalizable to breast cancer patients with micrometastases in their sentinel lymph node biopsy.

Long-term breast cancer survival in relation to the metastatic tumor burden in axillary lymph nodes.

PURPOSE: The clinical significance of lymph node micrometastases and isolated tumor cells (ITCs) in breast cancer is still controversial. After a median follow-up of 52 months, a report from the Swedish Multicenter Cohort Study presented a worse cancer-specific and event-free survival for patients with micrometastases than node-negative individuals, but could not demonstrate a significant difference in overall survival (OS). Due to the tendency of breast cancer to relapse after more than 5-10 years, we now report the long-term survival of the cohort. METHODS: Between September 2000 and January 2004, 3355 breast cancer patients were included in a prospective cohort. Sentinel lymph node biopsy was always performed. Patients were classified in four groups according to their overall nodal stage: node negative (N0, 2372), ITCs (113), micrometastases (123), and macrometastases (747). Kaplan-Meier survival estimates and Cox proportional hazard regression models were applied. RESULTS: Median follow-up was 156 months. Ten-year cancer-specific survival and OS were significantly lower in case of micrometastases than in N0 (84.7 vs. 93.5%, p = 0.001, and 75.5 vs. 84.2%, p = 0.046, respectively). In case of macrometastases, corresponding survival rates were 82.8 and 74.3%. Only for those aged less than 50 years, cancer-specific survival and OS were significantly worse in case of ITCs than N0. Patients with micrometastases received less often chemotherapy than those with macrometastases (24.4 vs. 53.9%). CONCLUSIONS: Lymph node micrometastases in breast cancer have a prognostic significance. This study demonstrates a similar survival for patients with micrometastases and those with macrometastases, possibly due to systemic undertreatment.

Breast-conserving surgery followed by whole-breast irradiation offers survival benefits over mastectomy without irradiation.

BACKGROUND: The prognostic equivalence between mastectomy and breast-conserving surgery (BCS) followed by radiotherapy was shown in pivotal trials conducted decades ago. Since then, detection and treatment of breast cancer have improved substantially and recent retrospective analyses point towards a survival benefit for less extensive breast surgery. Evidence for the association of such survival data with locoregional recurrence rates is largely lacking. METHODS: The Swedish Multicentre Cohort Study prospectively included clinically node-negative patients with breast cancer who had planned sentinel node biopsy between 2000 and 2004. Axillary lymph node dissection was undertaken only in patients with sentinel node metastases. For the present investigation, adjusted survival analyses were used to compare patients who underwent BCS and postoperative radiotherapy with those who received mastectomy without radiotherapy. RESULTS: Of 3518 patients in the Swedish Multicentre Cohort Study, 2767 were included in the present analysis; 2338 had BCS with postoperative radiotherapy and 429 had mastectomy without radiotherapy. Median follow-up was 156 months. BCS followed by whole-breast irradiation was superior to mastectomy without irradiation in terms of both overall survival (79·5 versus 64·3 per cent respectively at 13 years; P < 0·001) and breast cancer-specific survival (90·5 versus 84·0 per cent at 13 years; P < 0·001). The local recurrence rate did not differ between the two groups. The axillary recurrence-free survival rate at 13 years was significantly lower after mastectomy without irradiation (98·3 versus 96·2 per cent; P < 0·001). CONCLUSION: The present data support the superiority of BCS with postoperative radiotherapy over mastectomy without radiotherapy. The axillary recurrence rate differed significantly, and could be one contributing factor in a complex explanatory model.

Risk of recurrence and death in patients with breast cancer after delayed deep inferior epigastric perforator flap reconstruction.

BACKGROUND: Postmastectomy reconstruction using a deep inferior epigastric perforator (DIEP) flap is increasingly being performed in patients with breast cancer. The procedure induces extensive tissue trauma, and it has been hypothesized that the release of growth factors, angiogenic agonists and immunomodulating factors may reactivate dormant micrometastasis. The aim of the present study was to estimate the risk of breast cancer recurrence in patients undergoing DIEP flap reconstruction compared with that in patients treated with mastectomy alone. METHODS: Each patient who underwent delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013, was compared with up to four controls with breast cancer who did not receive a DIEP flap. The control patients were selected using incidence density matching with respect to age, tumour and nodal status, neoadjuvant therapy and year of mastectomy. The primary endpoint was breast cancer-specific survival. Survival analysis was carried out using Kaplan-Meier survival estimates and Cox proportional hazard regression analysis. RESULTS: The analysis included 250 patients who had 254 DIEP flap reconstructions and 729 control patients. Median follow-up was 89 and 75 months respectively (P = 0·053). Breast cancer recurrence developed in 50 patients (19·7 per cent) in the DIEP group and 174 (23·9 per cent) in the control group (P = 0·171). The 5-year breast cancer-specific survival rate was 92·0 per cent for patients with a DIEP flap and 87·9 per cent in controls (P = 0·032). Corresponding values for 5-year overall survival were 91·6 and 84·7 per cent (P < 0·001). After adjustment for tumour and patient characteristics and treatment, patients without DIEP flap reconstruction had significantly lower overall but not breast cancer-specific survival. CONCLUSION: The present findings do not support the hypothesis that patients with breast cancer undergoing DIEP flap reconstruction have a higher rate of breast cancer recurrence than those who have mastectomy alone.

Ten-year report on axillary recurrence after negative sentinel node biopsy for breast cancer from the Swedish Multicentre Cohort Study.

BACKGROUND: The omission of axillary lymph node dissection (ALND) in patients with breast cancer with a negative finding on sentinel node biopsy (SNB) has reduced arm morbidity substantially. Early follow-up reports have shown the rate of axillary recurrence to be significantly lower than expected, with a median false-negative rate of 7 per cent for SNB. Long-term follow-up is needed as recurrences may develop late. METHODS: The Swedish Multicentre Cohort Study included 3518 women with breast cancer and a clinically negative axilla, in whom SNB was planned. ALND was performed only in patients with sentinel node metastasis. Twenty-six centres contributed to enrolment between September 2000 and January 2004. The primary endpoint was the axillary recurrence rate and the secondary endpoint was breast cancer-specific survival, calculated using Kaplan-Meier survival estimates. RESULTS: Some 2216 sentinel node-negative patients with 2237 breast cancers were analysed. The median follow-up time was 126 (range 0-174) months. Isolated axillary recurrence was found in 35 patients (1·6 per cent). High histological grade and multifocal tumours were risk factors for axillary recurrence, whereas the removal of more than two sentinel nodes decreased the risk. Fourteen (40 per cent) of 35 patients died as a consequence of axillary recurrence. CONCLUSION: The risk of axillary recurrence remains lower than expected after a negative finding on SNB at 10-year follow-up. Axillary recurrences may occur long after primary surgery, and lead to a significant risk of breast cancer death.

Population-based analysis of colorectal cancer risk after oophorectomy.

BACKGROUND: The development of colorectal cancer is influenced by hormonal factors. Oophorectomy alters endogenous levels of sex hormones, but the effect on colorectal cancer risk is unclear. The aim of this cohort study was to examine colorectal cancer risk after oophorectomy for benign indications. METHODS: Women who had undergone oophorectomy between 1965 and 2011 were identified from the Swedish Patient Registry. Standard incidence ratios (SIRs) and 95 per cent confidence intervals for colorectal cancer risk were calculated compared with those in the general population. Stratification was carried out for unilateral and bilateral oophorectomy, and hysterectomy without specification of whether the ovaries were removed or not. Associations between the three oophorectomy options and colorectal cancer risk in different locations were assessed by means of hazard ratios (HRs) and 95 per cent confidence intervals calculated by Cox proportional hazards regression modelling. RESULTS: Of 195 973 women who had undergone oophorectomy, 3150 (1·6 per cent) were diagnosed with colorectal cancer at a later date (median follow-up 18 years). Colorectal cancer risk was increased after oophorectomy compared with that in the general population (SIR 1·30, 95 per cent c.i. 1·26 to 1·35). The risk was lower for younger age at oophorectomy (15-39 years: SIR 1·10, 0·97 to 1·23; 40-49 years: SIR 1·26, 1·19 to 1·33; P for trend < 0·001). The risk was highest 1-4 years after oophorectomy (SIR 1·66, 1·51 to 1·81; P < 0·001). In the multivariable analysis, women who underwent bilateral oophorectomy had a higher risk of rectal cancer than those who had only unilateral oophorectomy (HR 2·28, 95 per cent c.i. 1·33 to 3·91). CONCLUSION: Colorectal cancer risk is increased after oophorectomy for benign indications.

Oestrogen receptors ß1 and ßcx have divergent roles in breast cancer survival and lymph node metastasis.

BACKGROUND: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERß1, and its splice variant ERßcx is still unclear. METHODS: We here report an assessment of ERα, ERß1 and ERßcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes. RESULTS: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERß1 and ERßcx were equally distributed among age groups and tumour histological grades. Loss of ERß1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERß1. ERßcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes. CONCLUSIONS: Our study reveals highly significant although antagonising roles of ERß1 and ERßcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERß1 is of value as a prognostic and potentially predictive biomarker.

Arm lymphoedema after axillary surgery in women with invasive breast cancer.

BACKGROUND: The primary aim was to compare arm lymphoedema after sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND) in women with node-negative and node-positive breast cancer. The secondary aim was to examine the potential association between self-reported and objectively measured arm lymphoedema. METHODS: Women who had surgery during 1999-2004 for invasive breast cancer in four centres in Sweden were included. The study groups were defined by the axillary procedure performed and the presence of axillary metastases: SLNB alone, ALND without axillary metastases, and ALND with axillary metastases. Before surgery, and 1, 2 and 3 years after operation, arm volume was measured and a questionnaire regarding symptoms of arm lymphoedema was completed. A mixed model was used to determine the adjusted mean difference in arm volume between the study groups, and generalized estimating equations were employed to determine differences in self-reported arm lymphoedema. RESULTS: One hundred and forty women had SLNB alone, 125 had node-negative ALND and 155 node-positive ALND. Women who underwent SLNB had no increase in postoperative arm volume over time, whereas both ALND groups showed a significant increase. The risk of self-reported arm lymphoedema 1, 2 and 3 years after surgery was significantly lower in the SLNB group compared with that in both ALND groups. Three years after surgery there was a significant association between increased arm volume and self-reported symptoms of arm lymphoedema. CONCLUSION: SLNB is associated with a minimal risk of increased arm volume and few symptoms of arm lymphoedema, significantly less than after ALND, regardless of lymph node status.

Causes of false-negative sentinel node biopsy in patients with breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection as the routine staging procedure in clinically node-negative breast cancer. False-negative SLN biopsy results in misclassification and may cause undertreatment of the disease. The aim of this study was to investigate whether serial sectioning of SLNs reveals metastases more frequently in patients with false-negative SLNs than in patients with true-negative SLNs. METHODS: This was a case-control study. Tissue blocks from patients with false-negative SLNs, defined as tumour-positive lymph nodes excised at completion axillary dissection or a subsequent axillary tumour recurrence, were reassessed by serial sectioning and immunohistochemical staining. For each false-negative node, two true-negative SLN biopsies were analysed. Tumour and node characteristics in patients with false-negative SLNs were compared with those in patients with a positive SLN by univariable and multivariable regression analysis. RESULTS: Undiagnosed SLN metastases were discovered in nine (18 per cent) of 50 patients in the false-negative group and in 12 (11.2 per cent) of 107 patients in the true-negative group (P = 0.245). The metastases were represented by isolated tumour cells in 14 of these 21 patients. The risk of a false-negative SLN was higher in patients with hormone receptor-negative (odds ratio (OR) 2.50, 95 per cent confidence interval 1.17 to 5.33) or multifocal tumours (OR 3.39, 1.71 to 6.71), or if only one SLN was identified (OR 3.57, 1.98 to 6.45). CONCLUSION: SLN serial sectioning contributes to a higher rate of detection of SLN metastasis. The rate of upstaging of the tumour is similar in false- and true-negative groups of patients.

Axillary recurrence rate 5 years after negative sentinel node biopsy for breast cancer.

BACKGROUND: Sentinel lymph node (SLN) biopsy has replaced axillary lymph node dissection (ALND) as the standard axillary staging procedure in breast cancer. Follow-up studies in SLN-negative women treated without ALND report low rates of axillary recurrence, but most studies have short follow-up, and few are multicentre studies. METHODS: Between September 2000 and January 2004, patients who were SLN-negative and did not have ALND were included in a prospective cohort. Kaplan-Meier estimates were used to analyse the rates of axillary recurrence and survival. The risk of axillary recurrence was also compared in centres with high and low experience with the SLN biopsy (SLNB) technique. RESULTS: A total of 2195 patients with 2216 breast tumours were followed for a median of 65 months. Isolated axillary recurrence was diagnosed in 1·0 per cent of patients. The event-free 5-year survival rate was 88·8 per cent and the overall 5-year survival rate 93·1 per cent. There was no difference in recurrence rates between centres contributing fewer than 150 SLNB procedures to the cohort and centres contributing 150 or more procedures. CONCLUSION: This study confirmed the low risk of axillary recurrence 5 years after SLNB for breast cancer without ALND.

Immediate reconstruction with implants in women with invasive breast cancer does not affect oncological safety in a matched cohort study.

Physicians are still concerned about the oncological safety regarding immediate breast reconstruction (IBR) in breast cancer patients. This study aimed to evaluate possible differences between local, regional, and distant recurrences between women having implant-based reconstruction versus women operated with mastectomy alone. Secondary aims were to evaluate time to oncological treatment as well as disease-free and breast-cancer-specific survival. In a retrospective cohort designed study, 300 reconstructed patients with invasive breast cancer were matched with 300 patients from the population-based Regional Breast Cancer Register of the Stockholm-Gotland health-care region operated with mastectomy alone. They were matched for age, tumor size, nodal stage, and year of operation. Also included were patients treated with neoadjuvant chemotherapy and postoperative radiotherapy. The median follow-up for both the groups was 11.5 years (range 2-20). There were no significant differences in the local recurrence rate, 8.2% in the IBR group and 9.0% in the control group or in the regional recurrence rate, 8.2% versus 9.7%. Distant metastases occurred more frequently in the control group (27.1%) when compared to the IBR group (20.3%). There were no significant differences in time to treatment or in complications rate. Breast cancer mortality was 17% for the IBR group and 23% in the control group during follow-up. This long-term follow-up survey with a well-matched control group demonstrates that IBR with implants is safe to offer patients with invasive breast cancer without any negative effect on the oncological safety.

Survival in breast cancer patients with a delayed DIEP flap breast reconstruction after adjustment for socioeconomic status and comorbidity.

PURPOSE: Overall survival in breast cancer patients receiving a delayed deep inferior epigastric perforator (DIEP) flap breast reconstruction is better than in those without delayed breast reconstruction. This study aimed at determining the impact of socioeconomic status (SES) and comorbidity on these observations. MATERIALS AND METHODS: This matched cohort study included all consecutive women undergoing a delayed DIEP flap reconstruction at Karolinska University Hospital, Sweden, between 1999 and 2013. Controls had not received any delayed breast reconstruction and were relapse-free after a corresponding follow-up interval. Matching was by year of and age at mastectomy, tumour stage and lymph node status. Charlson Comorbidity Index (CCI) and socioeconomic data were obtained from national registers. Associations with breast cancer-specific (BCSS) and overall survival (OS) were investigated by Kaplan-Meier survival estimates and Cox proportional hazard regression analysis. RESULTS: Women in the DIEP group (N = 254) more often continued education after primary school (88.6% versus 82.6%, P = 0.026), belonged to the high-income group (76.0% versus 63.1%, P < 0.001), were in a partnership (57.1% versus 55.7%, P = 0.024) and healthier (median CCI 1.00 (range 0-13) versus 2.00 (range 0-16), P = 0.021) than the control group (N = 729). After adjustment for tumour and treatment factors, SES and comorbidity, OS remained significantly better for the DIEP group than the control group (HR 2.27, 95% CI 1.44-3.55). CONCLUSION: Women with a delayed DIEP flap reconstruction are a subgroup of higher socioeconomic status and better health. Higher survival estimates for the DIEP group persisted after adjusting for those differences, suggesting the presence of further unmeasured covariates.

Quality of life and patient satisfaction after implant-based breast reconstruction with or without acellular dermal matrix: randomized clinical trial.

BACKGROUND: Acellular dermal matrix (ADM) in implant-based breast reconstructions (IBBRs) aims to improve cosmetic outcomes. Six-month data are presented from a randomized trial evaluating whether IBBR with ADM provides higher health-related quality of life (HRQoL) and patient-reported cosmetic outcomes compared with conventional IBBR without ADM. METHODS: In this multicentre open-label RCT, women with breast cancer planned for mastectomy with immediate IBBR in four centres in Sweden and one in the UK were allocated randomly (1 : 1) to IBBR with or without ADM. HRQoL, a secondary endpoint, was measured as patient-reported outcome measures (PROMs) using three validated instruments (EORTC-QLQC30, QLQ-BR23, QLQ-BRR26) at baseline and 6 months. RESULTS: Between 24 April 2014 and 10 May 2017, 135 women were enrolled, of whom 64 with and 65 without ADM were included in the final analysis. At 6 months after surgery, patient-reported HRQoL, measured with generic QLQ-C30 or breast cancer-specific QLQ-BR23, was similar between the groups. For patient-reported cosmetic outcomes, two subscale items, cosmetic outcome (8·66, 95 per cent c.i. 0·46 to 16·86; P = 0·041) and problems finding a well-fitting bra (-13·21, -25·54 to -0·89; P = 0·038), yielded higher scores in favour of ADM, corresponding to a small to moderate clinical difference. None of the other 27 domains measured showed any significant differences between the groups. CONCLUSION: IBBR with ADM was not superior in terms of higher levels of HRQoL compared with IBBR without ADM. Although two subscale items of patient-reported cosmetic outcomes favoured ADM, the majority of cosmetic items showed no significant difference between treatments at 6 months. Registration number: NCT02061527 ( www.clinicaltrials.gov).

ANTECEDENTES: Se ha propuesto la utilización de mallas dérmicas acelulares (acellular dermal matrix, ADM) en las reconstrucciones mamarias con prótesis (implant'based breast reconstructions, IBBR) como forma de mejorar los resultados estéticos. Se presentan los resultados a 6 meses de un ensayo aleatorizado, que evaluó si la IBBR con ADM proporcionaba mejor calidad de vida relacionada con la salud (health'related quality of life, HRQOL) y mejores resultados estéticos percibidos por la paciente en comparación con la IBBR convencional sin ADM. MÉTODOS: Se ha propuesto la utilización de mallas dérmicas acelulares (acellular dermal matrix, ADM) en las reconstrucciones mamarias con prótesis (implant'based breast reconstructions, IBBR) como forma de mejorar los resultados estéticos. Se presentan los resultados a 6 meses de un ensayo aleatorizado, que evaluó si la IBBR con ADM proporcionaba mejor calidad de vida relacionada con la salud (health'related quality of life, HRQOL) y mejores resultados estéticos percibidos por la paciente en comparación con la IBBR convencional sin ADM. RESULTADOS: Entre el 24 de abril de 2014 y el 10 de mayo de 2017, se consideraron 135 mujeres, de las que se incluyeron en el análisis final 64 con ADM y 65 sin ADM. A los 6 meses de la intervención, la HRQOL medida con los cuestionarios QLQ-C30 (genérico) y QLQ-BR23 (específico para el cáncer de mama) fue similar en los dos grupos. Con respecto a los resultados estéticos percibidos por la paciente, se obtuvieron mejores puntuaciones a favor de la ADM en dos sub-escalas: "resultado estético" (8,66, i.c. del 95%, 0,46-16,86, P = 0,041) y "problemas para encontrar un sujetador que se ajuste bien" −13,21 (i.c. del 95% −25, 54 a −0,89, P = 0,038), lo que representa una diferencia clínica pequeña-moderada. No hubo diferencias significativas entre los dos grupos en ninguno de los otros 27 dominios medidos. CONCLUSIÓN: No se pudo demostrar la superioridad de la IBBR con ADM mediante variables relacionadas con la calidad de vida. Aunque se obtuvieron mejores puntuaciones con la ADM en dos sub-escalas de los PROMs, no hubo diferencias entre ambos tratamientos en la mayoría de las variables estéticas a los 6 meses.

Differences in endpoints between the Swedish W-E (two county) trial of mammographic screening and the Swedish overview: methodological consequences.

OBJECTIVES: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention. SETTING: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination. METHOD: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths. RESULTS: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest. CONCLUSIONS: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

Sentinel node biopsy in non-palpable breast cancer and in patients with a previous diagnostic excision.

AIM: As a means of staging the axilla with minimal surgical trauma, sentinel lymph node biopsy (SNB) has dramatically altered the management of early-stage breast cancer. The aim of this prospective multicentre study was to assess the safety of the method in cases of non-palpable tumours and in cases with an open biopsy prior to SNB. METHOD: In the period 1999-2001, 57 non-palpable breast cancers and 75 patients with diagnostic biopsy were collected prospectively to the first part of the study. In the second part, 745 patients with non-palpable breast cancers and 86 cases with prior open surgery diagnosed between 2000 and 2005 were followed up till the end of 2005. All patients in the first part of the study had an axillary clearance irrespective of sentinel node status, whereas in the second part axillary clearance was done only if the sentinel node was metastatic. RESULTS: The detection rate was 95% in the group of non-palpable breast cancers, with a false negative rate of 5.6% (1/18), and the corresponding figures for the group with prior intervention were 96% and 10% (2/20). Two axillary recurrences, after a negative SNB at primary surgery, were found in the non-palpable group after 16 and 17 months, respectively. No axillary recurrence has been observed in the group of cancers with a prior open biopsy. Four women in the non-palpable group and two women with a diagnostic operation experienced distant metastases. CONCLUSION: We conclude that SNB is a safe procedure for women with non-palpable breast cancer, as well as after previous open diagnostic excision.

Intraoperative sentinel lymph node examination by frozen section, immunohistochemistry and imprint cytology during breast surgery--a prospective study.

The aim of this study was to compare the sensitivity of intraoperative frozen section with hematoxyllin-eosin (H&E) staining, immunohistochemistry (IHC) or imprint cytology (IC) in the analysis of sentinel node (SN) in breast cancer. Towards this end, a prospective study of 102 patients undergoing mastectomy or sector resection with SN biopsy was conducted. Frozen sections of SN with H&E, IHC staining and IC had sensitivities of 73.5%, 75.5% and 51.0%, respectively. The combination of H&E and IHC raised the overall sensitivity to 83.7%. Macrometastases (>2 mm) were detected in 100% of the cases with H&E, 92.6% with IHC and 81.5% with IC; and micrometastases (2 mm) in 35.0%, 45.0% and 5.0%, respectively. The combination of H&E and IHC staining raised the sensitivity to 55.0%. Frozen-section analysis with H&E staining showed high sensitivity in detecting macrometastases but not micrometastases. The sensitivity for detection of micrometastases was not substantially increased by the use of intraoperative IHC. Imprint cytology did not provide any additional information.

Self-perceived, but not objective lymphoedema is associated with decreased long-term health-related quality of life after breast cancer surgery.

BACKGROUND: The primary aim was to compare long-term health-related quality of life (HRQoL) in patients undergoing sentinel lymph node biopsy (SLNB) alone versus axillary lymph node dissection (ALND), with or without axillary metastases. Secondary aims were to a) investigate agreement between objectively measured and self-reported lymphoedema and b) compare, with respect to HRQoL, women with objective arm lymphoedema without subjective ratings and those with no objective but subjective ratings of arm lymphoedema. METHODS: The three study groups were defined by axillary surgery: 1) SLNB alone (N = 140), 2) ALND in patients without axillary metastases (N = 125) and 3) ALND in patients with axillary metastases (N = 155). Preoperatively, one and three years postoperatively arm volume was measured and questionnaires regarding self-perceived symptoms of arm lymphoedema and HRQoL were completed (The Swedish Short Form-36 Health Survey, SF-36). RESULTS: Out of the original 516 who had axillary surgery, 420 (81%) completed the study. There were no statistically significant differences in HRQoL between the three study groups. No statistically significant agreement was found between self-perceived and objectively measured arm lymphoedema. Women without self-perceived arm lymphoedema, regardless of objective arm lymphoedema or not, scored higher on all eight SF-36 domains than those who reported self-perceived arm lymphoedema. CONCLUSION: Women reporting self-perceived arm lymphoedema, regardless of objective lymphoedema or not, have a decreased long-term health-related quality of life. This indicates that more attention should be given to the subjective reports of symptom in order to better help these women.