The diagnosis and management of pre-invasive breast disease: editor's reply

Introduction: The letter from Badve [1] relating to the series on pre-invasive breast disease, published in the September and November issues of Breast Cancer Research [2-10], is timely and very welcome. It rightly points out that one should be careful in changing classification systems based on limited knowledge and that perhaps discarding the term atypical ductal hyperplasia at the present time may be premature. I completely agree with him; however, there are a few issues I feel obliged to clarify

The value of mastectomy flap fixation in reducing fluid drainage and seroma formation in breast cancer patients

<p>Abstract</p> <p>Background</p> <p>Prolonged and excessive drainage of serous fluid and seroma formation constitute the most common complications after mastectomy for breast carcinoma. Seroma formation delays wound healing, increases susceptibility to infection, skin flap necrosis, persistent pain and prolongs convalescence. For this, several techniques have been investigated to improve primary healing and minimize seroma formation.</p> <p>Materials and methods</p> <p>Between June 2009 and July 2010 forty patients with breast carcinoma, scheduled for modified radical mastectomy, were randomly divided into 2 groups, the study group (20) and the control group (20). In the study group; the mastectomy flaps were fixed to the underlying muscles in raws, at various parts of the flap and at the wound edge using fine absorbable sutures. In the control group; the wound was closed in the conventional method at the edges. Closed suction drains were used in both groups. Patients, tumor characteristics and operative related factors were recorded. The amount and color of drained fluid were recorded daily. The drains were removed when the amount become less than 50 cc. The total amount and duration of drained fluid and the formation of seroma were recorded and the results were compared between the two groups.</p> <p>Results</p> <p>In the flap fixation group, the drain was removed in significantly shorter time compared to the control group (p < 0.001). Also, the total amount of fluid drained was significantly lower in the flap fixation group (p < 0.001). The flap fixation group showed a significantly lower frequency of seroma formation compared to the control group, both clinically (p = 0.028) and ultrasonographically (p = 0.047).</p> <p>Conclusions</p> <p>The mastectomy flap fixation technique is a valuable procedure that significantly decreases the incidence of seroma formation, and reduces the duration and amount of drained fluid. However, it should be tried on a much wider scale to prove its validity.</p

A Longitudinal Comparison of Arm Morbidity in Stage I–II Breast Cancer Patients Treated with Sentinel Lymph Node Biopsy, Sentinel Lymph Node Biopsy Followed by Completion Lymph Node Dissection, or Axillary Lymph Node Dissection

Background:\ud Long-term shoulder and arm function following sentinel lymph node biopsy (SLNB) may surpass that following complete axillary lymph node dissection (CLND) or axillary lymph node dissection (ALND). We objectively examined the morbidity and compared outcomes after SLNB, SLNB + CLND, and ALND in stage I/II breast cancer patients.\ud \ud Materials and Methods:\ud Breast cancer patients who had SLNB (n = 51), SLNB + CLND (n = 55), and ALND (n = 65) were physically examined 1 day before surgery (T0), and after 6 (T1), 26 (T2), 52 (T3), and 104 (T4) weeks. Differences in 8 parameters between the affected and unaffected arms were calculated. General linear models were computed to examine time, group, and interaction effects.\ud \ud Results:\ud All outcomes changed significantly, mostly nonlinearly, over time (T0–T4). Between T1 and T4, limitations decreased in abduction (all groups); anteflexion, abduction-exorotation, abduction strength (SLNB + CLND, ALND); flexion strength (SLNB + CLND); and arm volume (SLNB, SLNB + CLND). At T4, limitations in anteflexion (SLNB, ALND), abduction (SLNB + CLND, ALND), exorotation (ALND), abduction-exorotation (all groups), and volume (SLNB + CLND, ALND) increased significantly compared with T0. The SLNB group showed an advantage in anteflexion, abduction, abduction-exorotation, and volume. Groups changed significantly but differently over time in anteflexion, abduction, abduction/exorotation, abduction strength, flexion strength, and volume. Effect sizes varied from 0.19 to 0.00.\ud \ud Conclusion:\ud Initial declines in range of motion and strength were followed by recovery, although not always to presurgery levels. Range of motion and volume outcomes were better for SLNB than ALND, but not strength. SLNB surpassed SLNB + CLND in 2 of the range of motion variables. The clinical relevance of these results is negligible

A Buoyancy-Based Screen of Drosophila Larvae for Fat-Storage Mutants Reveals a Role for Sir2 in Coupling Fat Storage to Nutrient Availability

Obesity has a strong genetic component, but few of the genes that predispose to obesity are known. Genetic screens in invertebrates have the potential to identify genes and pathways that regulate the levels of stored fat, many of which are likely to be conserved in humans. To facilitate such screens, we have developed a simple buoyancy-based screening method for identifying mutant Drosophila larvae with increased levels of stored fat. Using this approach, we have identified 66 genes that when mutated increase organismal fat levels. Among these was a sirtuin family member, Sir2. Sirtuins regulate the storage and metabolism of carbohydrates and lipids by deacetylating key regulatory proteins. However, since mammalian sirtuins function in many tissues in different ways, it has been difficult to define their role in energy homeostasis accurately under normal feeding conditions. We show that knockdown of Sir2 in the larval fat body results in increased fat levels. Moreover, using genetic mosaics, we demonstrate that Sir2 restricts fat accumulation in individual cells of the fat body in a cell-autonomous manner. Consistent with this function, changes in the expression of metabolic enzymes in Sir2 mutants point to a shift away from catabolism. Surprisingly, although Sir2 is typically upregulated under conditions of starvation, Sir2 mutant larvae survive better than wild type under conditions of amino-acid starvation as long as sugars are provided. Our findings point to a Sir2-mediated pathway that activates a catabolic response to amino-acid starvation irrespective of the sugar content of the diet

Multifocality and multicentricity are not contraindications for sentinel lymph node biopsy in breast cancer surgery

BACKGROUND: After the availability of the results of validation studies, the sentinel lymph node biopsy (SLNB) has replaced routine axillary dissection (AD) as the new standard of care in early unifocal breast cancers. Multifocal (MF) and multicentric (MC) tumors have been considered a contraindication for this technique due to the possible incidence of a higher false-negative rate. This prospective study evaluates the lymphatic drainage from different tumoral foci of the breast and assesses the accuracy of SLNB in MF-MC breast cancer. PATIENTS AND METHODS: Patients with preoperative diagnosis of MF or MC infiltrating and clinically node-negative (cN0) breast carcinoma were enrolled in this study. Two consecutive groups of patients underwent SLN mapping using a different site of injection of the radioisotope tracer: a) "2ID" Group received two intradermal (ID) injections over the site of the two dominant neoplastic nodules. A lymphoscintigraphic study was performed after each injection to evaluate the route of lymphatic spreading from different sites of the breast. b) "A" Group had periareolar (A) injection followed by a conventional lymphoscintigraphy. At surgery, both radioguided SLNB (with frozen section exam) and subsequent AD were planned, regardless the SLN status. RESULTS: A total 31 patients with MF (n = 12) or MC (n = 19) invasive, cN0 cancer of the breast fulfil the selection criteria. In 2 ID Group (n = 15) the lymphoscintigraphic study showed the lymphatic pathways from two different sites of the breast which converged into one major lymphatic trunk affering to the same SLN(s) in 14 (93.3%) cases. In one (6.7%) MC cancer two different pathways were found, each of them affering to a different SLN. In A Group (n = 16) lymphoscintigraphy showed one (93.7%) or two (6.3%) lymphatic channels, each connecting areola with one or more SLN(s). Identification rate of SLN was 100% in both Groups. Accuracy of frozen section exam on SLN was 96.8% (1 case of micrometastasis was missed). SLN was positive in 13 (41.9%) of 31 patients, including 4 cases (30.7%) of micrometastasis. In 7 of 13 (53.8%) patients the SLN was the only site of axillary metastasis. SLNB accuracy was 96.8% (30 of 31), sensitivity 92.8 (13 of 14), and false-negative rate 7.1% (1 of 14). Since the case of skip metastasis was identified by the surgeon intraoperatively, it would have been no impact in the clinical practice. CONCLUSION: Our lymphoscintigraphic study shows that axillary SLN represents the whole breast regardless of tumor location within the parenchyma. The high accuracy of SLNB in MF and MC breast cancer demonstrates, according with the results of other series published in the literature, that both MF and MC tumors do not represent a contraindication for SLNB anymore

Quality of Life After Sentinel Lymph Node Biopsy or Axillary Lymph Node Dissection in Stage I/II Breast Cancer Patients: A Prospective Longitudinal Study

Background:\ud Breast cancer patients’ quality of life (QoL) after surgery has been reported to improve significantly over time. Little is known about QoL recovery after sentinel lymph node biopsy (SLNB) in comparison to axillary lymph node dissection (ALND).\ud \ud Methods:\ud 175 of 195 stage I/II breast cancer patients completed the EORTC QLQ-C30: one day before surgery (T0) and after 6 (T1), 26 (T2), 52 (T3) and 104 (T4) weeks. Of these, 54 patients underwent SLNB, 56 SLNB+ALND and 65 ALND. General linear models and paired T-tests between T0–T4 and T1–T4 were computed. Complications, radiotherapy and systemic therapy were added to the model.\ud \ud Results:\ud Significant time effects were found on physical, role and emotional functioning. Physical and role functioning decreased between T0 and T1. At T4, SLNB patients’ functioning had increased to their T0 level; ALND (+/– SLNB) patients’ functioning had increased, but had not improved to T0 level. Emotional functioning increased linearly between T0 and T4. At T4, emotional functioning was significantly higher in all groups as compared with T0. No significant group or interaction (time × group) effects were found. Complications and chemotherapy had a significant negative effect on role, emotional and cognitive functioning. Complications had a significant effect on social functioning also. Effect sizes varied between 0.00 and 0.06.\ud \ud Conclusion:\ud Two years post surgery, breast cancer patients’ QoL is comparable to that shortly before surgery. Women rated their emotional functioning as even better. SLNB is not associated with a better QoL than ALND. However, undergoing systemic therapy and/or experiencing complications affects QoL negatively