Fiona MacNeill

Extreme loss of immunoreactive p-Akt and p-Erk1/2 during routine fixation of primary breast cancer

IntroductionVery few studies have investigated whether the time elapsed between surgical resection and tissue fixation or the difference between core-cut and excision biopsies impact on immunohistochemically measured biomarkers, including phosphorylated proteins in primary breast cancer. The aim of this study was to characterise the differences in immunoreactivity of common biomarkers that may occur (1) as a result of tissue handling at surgery and (2) between core-cuts and resected tumours.MethodsCore-cuts taken from surgical breast cancer specimens immediately after resection (sample A) and after routine X-ray of the excised tumour (sample B) were formalin-fixed and paraffin-embedded and compared with the routinely fixed resection specimen (sample C). The variation in immunohistochemical expression of Ki67, oestrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor 2 (HER2), p-Akt and p-Erk1/2 were investigated.ResultsTwenty-one tissue sets with adequate tumour were available. Median time between collection of core-cuts A and B was 30 minutes (range, 20 to 80 minutes). None of the markers showed significant differences between samples A and B. Similarly, Ki67, ER, PgR and HER2 did not differ significantly between core-cuts and main resection specimen, although there was a trend for lower resection values for ER (P = 0.06). However, p-Akt and p-Erk1/2 were markedly lower in resections than core-cuts (median, 27 versus 101 and 69 versus 193, respectively; both P < 0.0001 [two-sided]). This difference was significantly greater in mastectomy than in lumpectomy specimens for p-Erk1/2 (P = 0.01).ConclusionsThe delay in fixation in core-cuts taken after postoperative X-ray of resection specimens has no significant impact on expression of Ki67, ER, PgR, HER2, p-Akt or p-Erk1/2. However, extreme loss of phospho-staining can occur during routine fixation of resection specimens. These differences are likely attributable to suboptimal fixation and may have major repercussions for clinical research involving these markers.

Comparison of the Systemic and Intratumoral Effects of Tamoxifen and the Aromatase Inhibitor Vorozole in Postmenopausal Patients With Primary Breast Cancer

PURPOSE To determine biologic differences, if any, between presurgical endocrine treatment with an aromatase inhibitor (vorozole) and tamoxifen in patients with postmenopausal primary breast cancer. PATIENTS AND METHODS Randomization was to 12 weeks of 2.5 mg of vorozole per day or 20 mg of tamoxifen per day, both orally. Clinical response was assessed monthly together with serum sex hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrogens (E1, E2, and E1S), lipids, insulin-like growth factor-1 (IGF-1), and bone metabolites (CrossLaps CTx). Tissue samples for Ki67, apoptotic index (AI), estrogen receptor, and progesterone receptor were collected at 0, 2, and 12 weeks. RESULTS Ki67 fell by 58% and 43% (means) at 2 weeks in the vorozole and tamoxifen patients, respectively (P =.13). In the vorozole group, the correlations of proportional changes in Ki67 at 2 weeks with tumor volume changes and clinical response at 12 weeks were not significant (P =.09) and marginally significant (P =.04), respectively. Serum lipids did not differ between groups. Serum levels of EI, E2, and E1S were suppressed markedly by vorozole, whereas levels of SHBG increased and LH and FSH fell significantly with tamoxifen. IGF-1 levels fell significantly with tamoxifen (P =.001) compared with the nonsignificant rise with vorozole. Twelve-week CTx values fell by 19% with tamoxifen (P =.006) and rose by 11% with vorozole (P =.15). CONCLUSION The correlation with vorozole of Ki67 with volume and clinical response supports this as an intermediate marker. The nonsignificant effects on bone and lipid metabolism by the aromatase inhibitor may be important to consider for adjuvant and potential prevention strategies.

How safe is oncoplastic breast conservation?: Comparative analysis with standard breast conserving surgery

AIM Oncoplastic techniques are increasingly used to facilitate breast conservation and maintain breast aesthetics but evidence with regards to the oncological safety of oncoplastic breast conservation surgery (oBCS) remains limited. The aim of this study was to compare re-excision and local recurrence rates for oBCS with standard breast conserving surgery (sBCS). METHODS From June 2003 to Feb 2010 data was obtained from contemporaneously recorded electronic patient records on patients who had oBCS and sBCS within a single breast cancer centre. Re-excision rates and local recurrence rates were compared. RESULTS A total of 440 sBCS and 150 oBCS (in 146 women) were included in this study. Median tumour size and specimen weight was 21 mm and 67 g for oBCS and 18 mm and 40 g in the sBCS group (p < 0.001). Re-excision was 2.7% (4/150) and 13.4% (59/440) for oBCS and sBCS respectively (p < 0.001). At a median follow-up of 28 months, local relapse was 2.7% (4) and 2.2% (10) and distant relapse 1.3% (2) and 7.5% (33) for oBCS and sBCS respectively. CONCLUSIONS Oncoplastic breast conserving techniques decrease re-excision rates. Early follow up data suggests oncological outcomes of oncoplastic breast conservation surgery are similar to standard breast conservation.

Trends in the use of bilateral mastectomy in England from 2002 to 2011: retrospective analysis of hospital episode statistics

Objectives For healthy women at high risk of developing breast cancer, a bilateral mastectomy can reduce future risk. For women who already have unilateral breast cancer, removing the contralateral healthy breast is more difficult to justify. We examined trends in the number of women who had a bilateral mastectomy in England between 2002 and 2011. Design Retrospective cohort study using the Hospital Episode Statistics database. Setting NHS hospital trusts in England. Participants Women aged between 18 and 80 years who had a bilateral mastectomy (or a contralateral mastectomy within 24 months of unilateral mastectomy) with or without a diagnosis of breast cancer. Main outcome measures Number and incidence of women without breast cancer who had a bilateral mastectomy; number and proportion who had a bilateral mastectomy as their first breast cancer operation, and the proportion of those undergoing bilateral mastectomy who had immediate breast reconstruction. Results Among women without breast cancer, the number who had a bilateral mastectomy increased from 71 in 2002 to 255 in 2011 (annual incidence rate ratio 1.16, 95% CI 1.13 to 1.18). In women with breast cancer, the number rose from 529 to 931, an increase from 2% to 3.1% of first operations (OR for annual increase 1.07, 95% CI 1.05 to 1.08). Across both groups, rates of immediate breast reconstruction roughly doubled and reached 90% among women without breast cancer in 2011. Conclusions The number of women who had a bilateral mastectomy nearly doubled over the last decade, and more than tripled among women without breast cancer. This coincided with an increase in the use of immediate breast reconstruction.

Sentinel lymph node biopsy after previous axillary surgery: A review.

BACKGROUND The utility of axillary lymph node dissection (ALND) in the management of breast cancer is currently under close scrutiny. At primary diagnosis the use of sentinel lymph node biopsy (SLNB) has restricted ALND for proven nodal disease, however the management of the axilla at local (in-breast) relapse is less clearly defined with many undergoing routine ALND. This review examines the role of SLNB in the re-operative setting with the objective of developing an axillary management algorithm for use at in-breast local relapse, and restricting ALND to node-positive recurrent cancers. METHODS We reviewed published reports of SLNB at local relapse in women who had previously undergone axillary surgery either as lymph node biopsy, SLNB, axillary sampling (AS) or axillary lymph node dissection (ALND). RESULTS There have been no randomised trials. Six reports with 327 cases were identified; of which 61% (199/327) had previous SLNB or ALND with <9 nodes removed. There was an overall successful sentinel lymph node (SLN) localisation at re-operation of 69% (227/327), range of 51-100%. In patients who have previously had limited axillary surgery (<9 nodes removed), the rate of successful SLN localisation was 83% (165/199), range of 68-100% and 142/165 (86%, range 80-100%) were node negative. In these highly selected patients no axillary recurrences were noted in those who had a negative SLN at re-operation after 26-46 months follow up. CONCLUSION SLNB at in-breast relapse is feasible and safe with successful localisation related to the extent of previous axillary surgery.

Contralateral Prophylactic Mastectomy (CPM) Consensus Statement from the American Society of Breast Surgeons: Data on CPM Outcomes and Risks.

The American Society of Breast Surgeons (ASBrS) endorses the American Board of Internal Medicine’s Choosing Wisely campaign statement: “Don’t routinely perform a double mastectomy in patients who have a single breast with cancer.”1 However, women with a newly diagnosed unilateral breast cancer are increasingly opting for bilateral mastectomy. This has been seen in patients who are candidates for breast conservation who elect mastectomy as well as those requiring mastectomy for their index breast cancer.2 National rates of contralateral prophylactic mastectomy (CPM) in the United States have been increasing and this trend is continuing.2–4

Anaphylaxis to Patent Blue V: a case series.

Blue dyes such as Patent Blue V (PBV) have been used in medical procedures for decades, and in the United Kingdom they are routinely utilised in sentinel lymph node biopsy (SLNB) for staging the axilla in early breast cancer. However, it has long been recognised that such dyes are associated with anaphylaxis. It has recently been estimated in a prospective study that allergy to PBV occurs with a frequency of 0.9%. Since repeated SLNB (and therefore further exposure to PBV) is increasingly being advocated for the small proportion of patients who develop a local (in-breast) recurrence, and because anaphylaxis can be life-threatening, it is important that those individuals that are allergic to PBV are recognised on their first medical exposure. The measurement of serum mast-cell tryptase (MCT) and skin prick test (SPT) are used in the investigation of suspected anaphylaxis because positive results are supportive of type-1 mediated hypersensitivity. Here we report the clinical features, MCT results and SPT results that pertain to a series of four patients referred to our drug allergy clinic with suspected anaphylaxis following SLNB. We recommend that all patients that show clinical evidence of allergy following exposure to PBV are referred to a specialist drug allergy service for further evaluation to investigate the cause.

Mastectomy and reconstruction in stage IV breast cancer: A survey of UK breast and plastic surgeons

The number of women with stage IV disease who have breast reconstruction is small. The primary aim of this study was to examine opinions as to the appropriateness of breast reconstruction in this group. The Association of Breast Surgeons (ABS) and the British Association of Plastic Reconstructive and Aesthetic Surgeons (BAPRAS) were invited to take part in an online survey. Of the respondents, 78.7% would operate on the primary tumour. Plastic surgeons showed a propensity for immediate reconstruction compared to their breast surgery colleagues, and 26.3% of breast surgeons would not offer reconstruction at all. Immediate latissimus dorsi (LD) flap and implant were the favoured method in early stage disease with delayed LD and implant the most popular option for stage IV disease. As survival figures continue to improve, the number of patients requesting reconstruction is likely to increase. Further debate will be necessary in anticipation of future service development.

Breast implant associated anaplastic large cell lymphoma: The UK experience. Recommendations on its management and implications for informed consent

BACKGROUND Breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare, Non-Hodgkin lymphoma arising in the capsule of breast implants. BIA-ALCL presents as a recurrent effusion and/or mass. Tumours exhibit CD30 expression and are negative for Anaplastic Lymphoma Kinase (ALK). We report the multi-disciplinary management of the UK series and how the stage of disease may be used to stratify treatment. METHODS Between 2012 and 2016, 23 cases of BIA-ALCL were diagnosed in 15 regional centres throughout the UK. Data on breast implant surgeries, clinical features, treatment and follow-up were available for 18 patients. RESULTS The mean lead-time from initial implant insertion to diagnosis was 10 years (range: 3-16). All cases were observed in patients with textured breast implants or expanders. Fifteen patients with breast implants presented with stage I disease (capsule confined), and were treated with implant removal and capsulectomy. One patient received adjuvant chest-wall radiotherapy. Three patients presented with extra-capsular masses (stage IIA). In addition to explantation, capsulectomy and excision of the mass, all patients received neo-/adjuvant chemotherapy with CHOP as first line. One patient progressed on CHOP but achieved pathological complete response (pCR) with Brentuximab Vedotin. After a mean follow-up of 23 months (range: 1-56) all patients reported here remain disease-free. DISCUSSION BIA-ALCL is a rare neoplasm with a good prognosis. Our data support the recommendation that stage I disease be managed with surgery alone. Adjuvant chemotherapy may be required for more invasive disease and our experience has shown the efficacy of Brentuximab as a second line treatment.

Subcutaneous implant breast reconstruction: Time to reconsider?

Improvements in breast surgery techniques such as skin and nipple preserving mastectomy and innovative prosthetics (implants, acellular dermal matrices and meshes) is renewing interest in subcutaneous (pre-pectoral) implant reconstruction. The aim of this paper is to review the current literature in an attempt to provide a rationale that may support a return to subcutaneous implant placement, so minimising the pain and functional problems resulting from submuscular breast reconstruction.