Germline BRCA mutation and outcome in young-onset breast cancer (POSH): a prospective cohort study.

BACKGROUND: Retrospective studies provide conflicting interpretations of the effect of inherited genetic factors on the prognosis of patients with breast cancer. The primary aim of this study was to determine the effect of a germline BRCA1 or BRCA2 mutation on breast cancer outcomes in patients with young-onset breast cancer. METHODS: We did a prospective cohort study of female patients recruited from 127 hospitals in the UK aged 40 years or younger at first diagnosis (by histological confirmation) of invasive breast cancer. Patients with a previous invasive malignancy (except non-melanomatous skin cancer) were excluded. Patients were identified within 12 months of initial diagnosis. BRCA1 and BRCA2 mutations were identified using blood DNA collected at recruitment. Clinicopathological data, and data regarding treatment and long-term outcomes, including date and site of disease recurrence, were collected from routine medical records at 6 months, 12 months, and then annually until death or loss to follow-up. The primary outcome was overall survival for all BRCA1 or BRCA2 mutation carriers (BRCA-positive) versus all non-carriers (BRCA-negative) at 2 years, 5 years, and 10 years after diagnosis. A prespecified subgroup analysis of overall survival was done in patients with triple-negative breast cancer. Recruitment was completed in 2008, and long-term follow-up is continuing. FINDINGS: Between Jan 24, 2000, and Jan 24, 2008, we recruited 2733 women. Genotyping detected a pathogenic BRCA mutation in 338 (12%) patients (201 with BRCA1, 137 with BRCA2). After a median follow-up of 8·2 years (IQR 6·0-9·9), 651 (96%) of 678 deaths were due to breast cancer. There was no significant difference in overall survival between BRCA-positive and BRCA-negative patients in multivariable analyses at any timepoint (at 2 years: 97·0% [95% CI 94·5-98·4] vs 96·6% [95·8-97·3]; at 5 years: 83·8% [79·3-87·5] vs 85·0% [83·5-86·4]; at 10 years: 73·4% [67·4-78·5] vs 70·1% [67·7-72·3]; hazard ratio [HR] 0·96 [95% CI 0·76-1·22]; p=0·76). Of 558 patients with triple-negative breast cancer, BRCA mutation carriers had better overall survival than non-carriers at 2 years (95% [95% CI 89-97] vs 91% [88-94]; HR 0·59 [95% CI 0·35-0·99]; p=0·047) but not 5 years (81% [73-87] vs 74% [70-78]; HR 1·13 [0·70-1·84]; p=0·62) or 10 years (72% [62-80] vs 69% [63-74]; HR 2·12 [0·82-5·49]; p= 0·12). INTERPRETATION: Patients with young-onset breast cancer who carry a BRCA mutation have similar survival as non-carriers. However, BRCA mutation carriers with triple-negative breast cancer might have a survival advantage during the first few years after diagnosis compared with non-carriers. Decisions about timing of additional surgery aimed at reducing future second primary-cancer risks should take into account patient prognosis associated with the first malignancy and patient preferences. FUNDING: Cancer Research UK, the UK National Cancer Research Network, the Wessex Cancer Trust, Breast Cancer Now, and the PPP Healthcare Medical Trust Grant.

Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial.

BACKGROUND: Four previously published randomised clinical trials have shown that tamoxifen can reduce the risk of breast cancer in healthy women at increased risk of breast cancer in the first 10 years of follow-up. We report the long-term follow-up of the IBIS-I trial, in which the participants and investigators remain largely masked to treatment allocation. METHODS: In the IBIS-I randomised controlled trial, premenopausal and postmenopausal women 35-70 years of age deemed to be at an increased risk of developing breast cancer were randomly assigned (1:1) to receive oral tamoxifen 20 mg daily or matching placebo for 5 years. Patients were randomly assigned to the two treatment groups by telephone or fax according to a block randomisation schedule (permuted block sizes of six or ten). Patients and investigators were masked to treatment assignment by use of central randomisation and coded drug supply. The primary endpoint was the occurrence of breast cancer (invasive breast cancer and ductal carcinoma in situ), analysed by intention to treat. Cox proportional hazard models were used to assess breast cancer occurrence and mortality. The trial is closed to recruitment and active treatment is completed, but long-term follow-up is ongoing. This trial is registered with controlledtrials.com, number ISRCTN91879928. FINDINGS: Between April 14, 1992, and March 30, 2001, 7154 eligible women recruited from genetics clinics and breast care clinics in eight countries were enrolled into the IBIS-I trial and were randomly allocated to the two treatment groups: 3579 to tamoxifen and 3575 to placebo. After a median follow up of 16.0 years (IQR 14.1-17.6), 601 breast cancers have been reported (251 [7.0%] in 3579 patients in the tamoxifen group vs 350 [9.8%] in 3575 women in the placebo group; hazard ratio [HR] 0.71 [95% CI 0.60-0.83], p<0.0001). The risk of developing breast cancer was similar between years 0-10 (226 [6.3%] in 3575 women in the placebo group vs 163 [4.6%] in 3579 women in the tamoxifen group; hazard ratio [HR] 0.72 [95% CI 0.59-0.88], p=0.001) and after 10 years (124 [3.8%] in 3295 women vs 88 [2.6%] in 3343, respectively; HR 0.69 [0.53-0.91], p=0.009). The greatest reduction in risk was seen in invasive oestrogen receptor-positive breast cancer (HR 0.66 [95% CI 0.54-0.81], p<0.0001) and ductal carcinoma in situ (0.65 [0.43-1.00], p=0.05), but no effect was noted for invasive oestrogen receptor-negative breast cancer (HR 1.05 [95% CI 0.71-1.57], p=0.8). INTERPRETATION: These results show that tamoxifen offers a very long period of protection after treatment cessation, and thus substantially improves the benefit-to-harm ratio of the drug for breast cancer prevention. FUNDING: Cancer Research UK (UK) and the National Health and Medical Research Council (Australia).

Cognitive behavioural treatment for women who have menopausal symptoms after breast cancer treatment (MENOS 1): a randomised controlled trial.

BACKGROUND: Hot flushes and night sweats (HFNS) affect 65-85% of women after breast cancer treatment; they are distressing, causing sleep problems and decreased quality of life. Hormone replacement therapy is often either undesirable or contraindicated. Safe, effective non-hormonal treatments are needed. We investigated whether cognitive behavioural therapy (CBT) can help breast cancer survivors to effectively manage HFNS. METHODS: In this randomised controlled trial, we recruited women from breast clinics in London, UK, who had problematic HFNS (minimum ten problematic episodes a week) after breast-cancer treatment. Participants were randomly allocated to receive either usual care or usual care plus group CBT (1:1). Randomisation was done in blocks of 12-20 participants, stratifying by age (younger than 50 years, 50 years or older), and was done with a computer-generated sequence. The trial statistician and researchers collecting outcome measures were masked to group allocation. Group CBT comprised one 90 min session a week for 6 weeks, and included psycho-education, paced breathing, and cognitive and behavioural strategies to manage HFNS. Assessments were done at baseline, 9 weeks, and 26 weeks after randomisation. The primary outcome was the adjusted mean difference in HFNS problem rating (1-10) between CBT and usual care groups at 9 weeks after randomisation. Analysis of the primary endpoint was done by modified intention to treat. The trial is registered, ISRCTN13771934, and was closed March 15, 2011. FINDINGS: Between May 5, 2009, and Aug 27, 2010, 96 women were randomly allocated to group CBT (n=47) or usual care (n=49). Group CBT significantly reduced HFNS problem rating at 9 weeks after randomisation compared with usual care (mean difference -1·67, 95% CI -2·43 to -0·91; p<0·0001) and improvements were maintained at 26 weeks (mean difference -1·76, -2·54 to -0·99; p<0·0001). We recorded no CBT-related adverse events. INTERPRETATION: Group CBT seems to be a safe and effective treatment for women who have problematic HFNS after breast cancer treatment with additional benefits to mood, sleep, and quality of life. The treatment could be incorporated into breast cancer survivorship programmes and delivered by trained breast cancer nurses. FUNDING: Cancer Research UK.

An evidence based strategy for follow up after breast conserving treatment for breast cancer.

BACKGROUND AND OBJECTIVES: Follow up for breast cancer patients aims at the timely detection of loco-regional recurrences and contralateral breast cancers (LRR). This study investigates the annual risk of LRR after breast conserving treatment (BCT) and the potential value of mammographic surveillance and/or routine clinical examination. METHODS: Data on 650 women who underwent BCT were obtained and LRR was divided into parenchymal and non-parenchymal. LRR-free and cumulative LRR-free rates were calculated. In patients where recurrence was diagnosed at a routine clinic visit and had negative mammography ("clinical detection only" group) were also separately examined. RESULTS: Median follow up was 115 months, range 9-196. Seventy-three patients had parenchymal and 16 nodal recurrence. The median probability of LRR was 1.4% and of parenchymal LRR was 1.32% per year, remaining constant for up to 168 months. The 16 patients in the "clinical detection only" group relapsed mainly during the first 2 years (annual risk 0.77% and 0.80%, respectively). CONCLUSIONS: This study shows that the risk of parenchymal LRR remains constant for at least 14 years and is significant enough to warrant routine long-term follow up mammography. Routine clinical examination contributes significantly to the detection of LRR only for the first 2 years.

An update on granulomatous mastitis: a rare and complex condition.

Granulomatous mastitis is a rare inflammatory condition of the breast affecting women of child-bearing age. The disease is characterised by chronic and relapsing inflammation, resulting in scarring and discharging sinuses. Granulomatous mastitis is considered to be idiopathic and the pathogenesis is poorly understood. An amplified immune response has been proposed as a likely cause and there is evidence linking Corynebacterium to some cases of granulomatous mastitis. The presentation is similar to bacterial mastitis or abscess and antibiotics are commonly commenced empirically. The cornerstone of diagnosis is histopathological evaluation on core biopsy; an index of suspicion based on demographic assessment can avoid delays in diagnosis. Management is difficult and there is no consensus on best treatment. Various treatment regimens are described, with high relapse rates relating to the nature of the condition. Watchful waiting is appropriate for mild presentations and steroids are the mainstay of treatment for more severe cases. This article reviews the emerging evidence on granulomatous mastitis and describes an updated approach to management.

Continuity of Cancer Care: The Surgical Experience of Two Large Cancer Hubs in London and Milan.

The SARS-CoV-2 (COVID-19) pandemic is having a large effect on the management of cancer patients. This study reports on the approach and outcomes of cancer patients receiving radical surgery with curative intent between March and September 2020 (in comparison to 2019) in the European Institute of Oncology, IRCCS (IEO) in Milan and the South East London Cancer Alliance (SELCA). Both institutions implemented a COVID-19 minimal pathway where patients were required to self-isolate prior to admission and were swabbed for COVID-19 within 72 h of surgery. Positive patients had surgery deferred until a negative swab. At IEO, radical surgeries declined by 6% as compared to the same period in 2019 (n = 1477 vs. 1560, respectively). Readmissions were required for 3% (n = 41), and <1% (n = 9) developed COVID-19, of which only one had severe disease and died. At SELCA, radical surgeries declined by 34% (n = 1553 vs. 2336). Readmissions were required for 11% (n = 36), <1% (n = 7) developed COVID-19, and none died from it. Whilst a decline in number of surgeries was observed in both centres, the implemented COVID-19 minimal pathways have shown to be safe for cancer patients requiring radical treatment, with limited complications and almost no COVID-19 infections.

Wire guided localisation for targeted axillary node dissection is accurate in axillary staging in node positive breast cancer following neoadjuvant chemotherapy.

AIM: This study investigated whether wire localisation of the histologically proven positive, clipped axillary lymph node (ALN) with subsequent targeted axillary dissection (TAD) following neoadjuvant chemotherapy (NACT) improves axillary staging in breast cancer. MATERIALS AND METHODS: We performed a retrospective review of patients with primary breast cancer and core biopsy proven metastatic ALNs, that had an excellent nodal radiological response following NACT, treated at our centre between January 2016 and December 2018. The initial cohort of patients (Group 1) underwent sentinel lymph node biopsy (SLNB), with a minimum of three nodes were sampled. The subsequent cohort (Group 2) had a marker clip inserted in the metastatic ALN prior to NACT. This cohort underwent wire guided excision of the clipped node in addition to SLNB, with a minimum of three nodes sampled. RESULTS: A total of 47 patients were identified. Group 1 comprised 22 patients with a sentinel lymph node (SLN) identification rate (IR) of 95%. 25 patients (Group 2) underwent wire guided clip location and the SLN IR was 100% with a 92% clipped node IR. Evidence of pathological complete response (pCR) in the clipped node was associated with pCR in other nodes. CONCLUSION: Targeted axillary dissection is a feasible technique following excellent response to NACT in selected patients with limited volume ALN metastasis, at diagnosis. The identification of the positive ALN during surgery is vital and the IR can be improved by clipping the node prior to NACT and wire guided localisation at the time of surgery.

Evaluation of a group cognitive behavioural intervention for women suffering from menopausal symptoms following breast cancer treatment.

OBJECTIVE: To evaluate a group cognitive behavioural intervention to alleviate menopausal symptoms in women who have had treatment for breast cancer. METHODS: A single group design was used with pre- and post-treatment assessment and a 3-months follow-up. Seventeen women who had completed active breast cancer treatment were treated. Following a 2-week daily diary assessment they were offered 6 (90 min) weekly sessions of Group cognitive behaviour therapy (CBT). The CBT included information and discussion, relaxation and paced breathing and CBT to reduce stress and manage hot flushes (HF), night sweats (NS) and sleep. The primary outcome measure was Hot Flush Frequency and Hot Flush Problem Rating; secondary outcomes included the Women's Health Questionnaire (WHQ) and health-related quality of life (SF 36). Beliefs about HF were monitored in order to examine the effects of cognitive therapy. RESULTS: HF and NS reduced significantly following treatment (38% reduction in frequency and 49% in problem rating) and improvements were maintained at 3 months follow-up (49% reduction in frequency and 59% in problem rating). Depressed mood, anxiety and sleep (WHQ) significantly improved, as did aspects of quality of life (SF 36) (emotional role limitation, energy/vitality and mental health). There was a significant reduction in negative beliefs about HF, NS and sleep following CBT. CONCLUSIONS: These results suggest that CBT delivered in groups might offer a viable option for women with troublesome menopausal symptoms following breast cancer treatment, but further controlled trials are needed.

Genetics of breast cancer: management strategies and risk-reducing surgery.

The last two decades have witnessed major advances in genetic sequencing which have led to more accurate identification of women at risk of developing breast cancer and calculating the associated cancer risk. This review discusses the current genetic mutations conferring risk of developing breast cancer and the management pathway for these women with identifiable mutations as well as those with a strong family history for breast cancer. Management of these individuals is complex and should involve a multidisciplinary team with interest and expertise in breast cancer genetics. There are several treatment options ranging from surveillance to risk-reducing surgery. Risk reduction surgery has been popularised by celebrities who are carriers of breast cancer genes, and raised public awareness of breast cancer genetics and associated risk.

Intraoperative Assessment of Tumor Resection Margins in Breast-Conserving Surgery Using 18F-FDG Cerenkov Luminescence Imaging: A First-in-Human Feasibility Study.

In early-stage breast cancer, the primary treatment option for most women is breast-conserving surgery (BCS). There is a clear need for more accurate techniques to assess resection margins intraoperatively, because on average 20% of patients require further surgery to achieve clear margins. Cerenkov luminescence imaging (CLI) combines optical and molecular imaging by detecting light emitted by 18F-FDG. Its high-resolution and small size imaging equipment make CLI a promising technology for intraoperative margin assessment. A first-in-human study was conducted to evaluate the feasibility of 18F-FDG CLI for intraoperative assessment of tumor margins in BCS. Methods: Twenty-two patients with invasive breast cancer received 18F-FDG (5 MBq/kg) 45-60 min before surgery. Sentinel lymph node biopsy was performed using an increased 99mTc-nanocolloid activity of 150 MBq to facilitate nodal detection against the γ-probe background signal (cross-talk) from 18F-FDG. The cross-talk and 99mTc dose required was evaluated in 2 lead-in studies. Immediately after excision, specimens were imaged intraoperatively in an investigational CLI system. The first 10 patients were used to optimize the imaging protocol; the remaining 12 patients were included in the analysis dataset. Cerenkov luminescence images from incised BCS specimens were analyzed postoperatively by 2 surgeons blinded to the histopathology results, and mean radiance and margin distance were measured. The agreement between margin distance on CLI and histopathology was assessed. Radiation doses to staff were measured. Results: Ten of the 12 patients had an elevated tumor radiance on CLI. Mean radiance and tumor-to-background ratio were 560 ± 160 photons/s/cm2/sr and 2.41 ± 0.54, respectively. All 15 assessable margins were clear on CLI and histopathology. The agreement in margin distance and interrater agreement was good (κ = 0.81 and 0.912, respectively). Sentinel lymph nodes were successfully detected in all patients. The radiation dose to staff was low; surgeons received a mean dose of 34 ± 15 µSv per procedure. Conclusion: Intraoperative 18F-FDG CLI is a promising, low-risk technique for intraoperative assessment of tumor margins in BCS. A randomized controlled trial will evaluate the impact of this technique on reexcision rates.

Is blue dye still required during sentinel lymph node biopsy for breast cancer?

BACKGROUND: In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates. METHODS: Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique. RESULTS: A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients. CONCLUSION: The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation.

Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction.

UNLABELLED: Recent papers and guidelines agree that patients with locally advanced breast cancer (LABC) should be offered breast reconstruction. Yet, the type of reconstruction in this group of patients is still a point of controversy. METHODS: One hundred fourteen patients, treated for LABC from 2007 to 2013, were divided into 3 groups based on the reconstructive option: no reconstruction (NR), implant-based/expander-based reconstruction (IBR), and autologous tissue reconstruction (ATR). We analyzed demographics and compared delay in adjuvant therapy, length of hospitalization, surgical complications, failure of reconstruction, local recurrence, and disease-free survival. RESULTS: Twenty-six patients had NR, 38 had IBR, and 50 had ATR. No significant difference was found in the percentage of patients who had their adjuvant treatment delayed [16% (NR) vs 22% (IBR) vs 14% (ATR)]. Mean length of hospitalization for the NR, IBR, and ATR groups was 2.7, 6, and 7.5 days, respectively. Complication rates requiring readmission were 36% (NR), 42% (IBR), and 32% (ATR). In the IBR group, 37% of implants were removed because of complications. Failure of reconstruction was 37% and 0% for the IBR and ATR groups, respectively. Local recurrence rates in the NR and Reconstruction (groups IBR and ATR combined) groups were 7% and 2%, respectively. Mean survival times in patients were 18 (NR), 10.3 (IBR), and 12.2 (ATR) months. CONCLUSIONS: No significant difference was found in the hospital stay length, adjuvant treatment delay, and complication rates between IBR and ATR. High rates of failed reconstruction suggest that the use of implants should be considered very carefully in patients with LABC.

Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial.

BACKGROUND: Initial results from the first International Breast Cancer Intervention Study (IBIS-I) found that tamoxifen reduced the risk of invasive estrogen receptor (ER)-positive tumors by 31% in women at increased risk for breast cancer, but most of the follow-up at this time was during the active treatment phase. We report an updated analysis of IBIS-I that focuses on the period after active treatment was completed, a time for which little evidence from other trials is available. METHODS: A total of 7145 women who were aged 35-70 years and at increased risk of breast cancer were randomly assigned to receive either tamoxifen (20 mg/day) or placebo for 5 years. The primary outcome measure was the incidence of breast cancer (including ductal carcinoma in situ), but side effects were also investigated. Relative risks were computed as the ratio of incidence rates. All statistical tests were two-sided. RESULTS: After a median follow-up of 96 months after randomization, 142 breast cancers were diagnosed in the 3579 women in the tamoxifen group and 195 in the 3575 women in the placebo group (4.97 versus 6.82 per 1000 woman-years, respectively; risk ratio [RR] = 0.73, 95% confidence interval [CI] = 0.58 to 0.91, P = .004). The prophylactic effect of tamoxifen was fairly constant for the entire follow-up period, and no diminution of benefit was observed for up to 10 years after randomization. However, side effects in the tamoxifen group were much lower after completion of the active treatment period than during active treatment. For example, deep-vein thrombosis and pulmonary embolism were statistically significantly higher in the tamoxifen arm than in the placebo arm during active treatment (52 versus 23 cases, RR = 2.26, 95% CI = 1.36 to 3.87) but not after tamoxifen was stopped (16 versus 14 cases, RR = 1.14, 95% CI = 0.52 to 2.53). The two arms did not differ in the risk of ER-negative invasive tumors (35 in each arm, RR = 1.00, 95% CI = 0.61 to 1.65) across the entire follow-up period, but the risk of ER-positive invasive breast cancer was 34% lower in the tamoxifen arm (87 versus 132 cases, RR = 0.66, 95% CI = 0.50 to 0.87). CONCLUSIONS: The risk-reducing effect of tamoxifen appears to persist for at least 10 years, but most side effects of tamoxifen do not continue after the 5-year treatment period.

FPGA-based sleep apnea screening device for home monitoring.

We present the hardware design of an FPGA-based portable device for home screening of sleep apnea syndromes. The device is simple to use, inexpensive, and uses only three signals, namely the nasal air flow and the thorax and abdomen effort signals. The device hardware stores data of overnight sleep on a Secure Digital card. At the clinic, the sleep specialist reads in the stored data and uses an algorithm for the detection and classification of sleep apnea. The device is fairly low-cost and may help spread the ability to diagnose more cases of sleep apnea. Most sleep apnea cases currently go undiagnosed because of cost and practicality limitations of overnight polysomnography at sleep labs.

Menopausal symptoms in women with breast cancer: prevalence and treatment preferences.

Menopausal symptoms are common and problematic for women receiving adjuvant treatment for breast cancer and management presents a challenge. This cross-sectional descriptive study aimed to investigate the experience of menopausal symptoms, current management and treatment preferences of 113 patients with breast cancer. These women (who were prescribed tamoxifen and were on average 3 years post-diagnosis) were recruited from a breast unit database. They completed the Hot Flush and Night Sweats Questionnaire (HFNSQ), the Women's Health Questionnaire (WHQ) and subscales of the EORTC-QLQ-C30 and the BR23, as well as questions about treatments. Forty-four of this sample were also interviewed. The prevalence of hot flushes and night sweats was 80 and 72%, respectively (average 30 per week). Having more problematic hot flushes and night sweats were associated with more anxiety and sleep problems (WHQ), and with poorer emotional and social functioning and worse body image (EORTC-QLQ-C30). The women had used a range of treatments for menopausal symptoms but there was often no evidence for the efficacy for many of these treatments. Strongest preferences were for non-medical treatments, particularly vitamins and herbal remedies and cognitive behavioural therapy (CBT). The evidence for the effectiveness of the former is weak, whereas CBT has been shown to reduce menopausal symptoms, but needs to be evaluated in a population of women who have been treated for breast cancer.

Paget disease of the nipple: a multifocal manifestation of higher-risk disease.

BACKGROUND: The treatment of Paget disease by mastectomy has been challenged recently in favor of breast-conserving techniques. A large series of patients treated with mastectomy has been reviewed to assess the feasibility of less radical surgery. METHODS: The cases of 70 women with a clinical diagnosis of Paget disease were reviewed. The type, grade, receptor and node status, and the mammographic and pathologic extent of the underlying breast malignancy were determined. The survival of patients with invasive disease was compared with matched controls without Paget disease. RESULTS: The underlying malignancy was invasive in 58% of cases. Despite the fact that only one third of women presented with a palpable mass, the malignancy was frequently extensive, being confined to the retroareolar region in only 25% of cases. The true extent of the disease was underestimated by mammography in 43% of cases. Of the patients with ductal in situ carcinoma, 96.5% had high-grade carcinomas and 100% had invasive carcinomas of high cytonuclear grade. Overexpression of the c-erb-B2 oncogene was detectable in 83% of cases. Patients with Paget disease had a significantly worse survival than matched controls, but this difference was eliminated if they were also matched for c-erb-B2 status. CONCLUSIONS: Paget disease is often associated with extensive underlying malignancy, which is difficult to assess accurately either clinically or mammographically. As a consequence, cone excision of the nipple would have resulted in incomplete excision in 75% of cases. The underlying disease is of high grade and is frequently c-erb-B2 positive with a resulting poor prognosis. Aggressive local and systemic treatment would seem to be merited.

Breast carcinoma in women age 25 years or less.

BACKGROUND: Although several studies have examined breast carcinoma in young women aged < or = 35 years at diagnosis, there are only occasional cases reported in very young women aged < or = 25 years, and, to the authors' knowledge, no series are available. The presentation, tumor biology, behavior, and outcome of breast carcinoma in very young women are not known, and the rarity of breast malignancy within this age group could lead to diagnostic delays. METHODS: The tumor characteristics and survival of 15 women aged < or = 25 years at the time of diagnosis, have been reviewed and compared with women aged 26-35 years under the care of Guy's Hospital's Breast Unit during the same period of time. Where appropriate, the two groups were individually matched for tumor size (clinical measurement) and histologic grade. RESULTS: Fifteen cases were examined, with a median follow-up of 108 months and a median age of 24 years. The median duration of symptoms was 4 weeks, and the median tumor size was 20 mm. Two patients had ductal carcinoma in situ (DCIS) only, while the other 13 patients had invasive carcinomas, none of which were Grade I. A mastectomy was performed on 8 out of 15 patients (53%). Axillary nodal metastases were present in 4 out of 12 patients (33%). Of the 13 cases of invasive disease, 9 out of 13 patients (69%) experienced recurrence and died of breast carcinoma. Median disease free survival for patients with invasive disease was 86 months. There was no difference in overall survival between the patients aged < or = 25 years and those aged 26-35, but taken together young women < or = 35 had a worse prognosis than women between 36 and 65, due to a higher incidence of high grade and estrogen receptor negative tumors. CONCLUSIONS: The current study suggests that among young women with breast carcinoma there is no difference in prognosis between the very young and the young. Despite two thirds of patients being node negative, the high mortality rate indicates a need for an optimal selection of adjuvant therapy among these cases.

Punçäo aspirativa por agulha fina de lesöes mamárias usando dispositivo de auto-vácuo / Fine needle aspirations of breast lesions using auto-vacuum dispositive

Um novo dispositivo no qual uma mola é adaptada entre a seringa e seu êmbolo (dispositivo de auto-vácuo), foi testado para auxiliar a punçäo aspirativa por agulha fina. Após resultados encorajadores em cobaias, o sistema de auto-vácuo foi avaliado inicialmente na punçäo de 42 pacientes com nódulos de mama. Destas, 36 apresentaram confirmaçäo histológica de malignidade (89 por cento) e 11 por cento de benignidade. A sensibilidade foi 97 por cento, especificidade 100 por cento, valor preditivo positivo 100 por cento, valor preditivo negativo 67 por cento e acurácia total de 97 por cento. Concluiu-se que o sistema de auto-vácuo pode obter boas amostras para citologia, além de facilitar o procedimento.