Tuesday 4 July 2017

Rationale for immunological approaches to breast cancer therapy

Rationale for immunological approaches to breast cancer therapy

Monnot GC and Romero P
The Breast 
Article in Press

Despite great advances in early detection, as well as surgical resection of breast tumours, breast cancer remains the deadliest cancer for women worldwide. Moreover, its incidence is without pair, accounting for twice as many new cancer cases as the second most prevalent cancer, colorectal carcinoma. There is therefore a strong need for new therapeutic approaches to breast cancers. Immunotherapies are novel treatment modalities which aim to use immune mediators to attack cancerous cells. Recent clinical results show that these may not only mediate tumour regressions but also cures in some cases.

Evaluation of margins in invasive carcinoma and ductal carcinoma in situ: The pathologist's perspective

Evaluation of margins in invasive carcinoma and ductal carcinoma in situ: The pathologist's perspective

Schnitt SJ
The Breast 
Article in Press

A variety of patient factors, treatment factors and pathologic factors are associated with an increased risk of ipsilateral breast tumor recurrence (local recurrence) after breast conservation therapy for invasive breast cancer and ductal carcinoma in situ (DCIS). Arguably, the most important of these is the status of the microscopic margins of excision of the resected breast specimen. Until recently there has been no agreement on what constitutes an adequate negative lumpectomy margin for patients with either invasive breast cancer or DCIS managed with the breast conserving approach  and this issue has never been addressed in randomized clinical trials.

Postoperative radiotherapy after DCIS: Useful for whom?

Postoperative radiotherapy after DCIS: Useful for whom?

Karlsson P
The Breast 
Article in Press

The number of patients with ductal carcinoma in situ (DCIS) increases with more widely used screening mammography programs. DCIS accounts for approximately 20% of all new breast cancer diagnoses in these programs and the natural course of this heterogeneous group of pre-invasive lesions is not fully known. Better definition of subgroups benefitting from radiotherapy and knowledge on the natural course of DCIS are important issues for the future management of DCIS.Four large randomized trials have studied the effects of postoperative radiotherapy after breast conserving surgery in patients with wider spectrum of DCIS and all of them have shown radiotherapy to halve the risk of ipsilateral events, however, without any significant effect on breast cancer mortality.

Impact of Evolving Radiation Therapy Techniques on Implant-Based Breast Reconstruction

Impact of Evolving Radiation Therapy Techniques on Implant-Based Breast Reconstruction

Muresan, H et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1232e–1239e

Background: Patients undergoing implant-based reconstruction in the setting of postmastectomy radiation therapy suffer from increased complications and inferior outcomes compared with those not irradiated, but advances in radiation delivery have allowed for more nuanced therapy. The authors investigated whether these advances impact patient outcomes in implant-based breast reconstruction. 
Methods: Retrospective chart review identified all implant-based reconstructions performed at a single institution from November of 2010 to November of 2013. These data were cross-referenced with a registry of patients undergoing breast irradiation. Patient demographics, treatment characteristics, and outcomes were analyzed. 
Results: Three hundred twenty-six patients (533 reconstructions) were not irradiated, whereas 83 patients (125 reconstructions) received radiation therapy; mean follow-up was 24.7 months versus 26.0 months (p = 0.49). Overall complication rates were higher in the irradiated group (35.2 percent versus 14.4 percent; p < 0.01). Increased maximum radiation doses to the skin were associated with complications (maximum dose to skin, p = 0.05; maximum dose to 1 cc of skin, p = 0.01). Different treatment modalities (e.g., three-dimensional conformal, intensity-modulated, field-in-field, and hybrid techniques) did not impact complication rates. Prone versus supine positioning significantly decreased the maximum skin dose (58.5 Gy versus 61.7 Gy; p = 0.05), although this did not translate to significantly decreased complication rates in analysis of prone versus supine positioning. 
Conclusions: As radiation techniques evolve, the maximum dose to skin should be given consideration similar to that for heart and lung dosing, to optimize reconstructive outcomes. Prone positioning significantly decreases the maximum skin dose and trends toward significance in reducing reconstructive complications. With continued study, this may become clinically important. Interdepartmental studies such as this one ensure quality of care.

Comparing Health Care Resource Use between Implant and Autologous Reconstruction of the Irradiated Breast: A National Claims-Based Assessment

Comparing Health Care Resource Use between Implant and Autologous Reconstruction of the Irradiated Breast: A National Claims-Based Assessment

Aliu, O et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1224e–1231e

Background: In the debate on reconstruction of the irradiated breast, there is little information on associated health care resource use. Nationwide data were used to examine health care resource use associated with implant and autologous reconstruction. It was hypothesized that failure rates would contribute the most to higher average cumulative cost with either reconstruction method. 
Methods: From the 2009 to 2013 MarketScan Commercial Claims and Encounters database, irradiated breast cancer patients who underwent implant or autologous reconstruction were selected. In a 24-month follow-up period, the cumulative costs of health care services used were tallied and described. Regression models stratified by reconstruction method were then used to estimate the influence of failure on cumulative cost of reconstruction. 
Results: There were 2964 study patients. Most (78 percent) underwent implant reconstruction. The unadjusted mean costs for implant and autologous reconstructions were $22,868 and $30,527, respectively. Thirty-two percent of implant reconstructions failed, compared with 5 percent of autologous cases. Twelve percent of the implant reconstructions had two or more failures and required subsequent autologous reconstruction. The cost of implant reconstruction failure requiring a flap was $47,214, and the cost for autologous failures was $48,344. In aggregate, failures constituted more than 20 percent of the cumulative costs of implant reconstruction compared with less than 5 percent for autologous reconstruction. 
Conclusions: More than one in 10 patients who had implant reconstruction in the setting of radiation therapy to the breast eventually required a flap for failure. These findings make a case for autologous reconstruction being primarily considered in irradiated patients who have this option available.

Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies

Comparison of Outcomes with Tissue Expander, Immediate Implant, and Autologous Breast Reconstruction in Greater Than 1000 Nipple-Sparing Mastectomies

Frey, J et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1300–1310

Background: Nipple-sparing mastectomy permits complete preservation of the nipple-areola complex with excellent aesthetic results and with oncologic safety similar to that associated with traditional mastectomy techniques. However, outcomes have not been directly compared for tissue expander–, immediate implant–, and autologous tissue–based breast reconstruction after nipple-sparing mastectomy. Methods: All patients undergoing nipple-sparing mastectomy from 2006 to June of 2016 were identified at a single institution. Demographics and outcomes were analyzed and compared among different types of breast reconstruction. Results: A total of 1028 nipple-sparing mastectomies were performed. Of these, 533 (51.8 percent) were tissue expander–based, 263 (25.6 percent) were autologous tissue–based, and 232 (22.6 percent) were immediate implant–based reconstructions. Tissue expander–based reconstructions had significantly more minor cellulitis (p = 0.0002) but less complete nipple necrosis (p = 0.0126) and major mastectomy flap necrosis (p < 0.0001) compared with autologous tissue–based reconstructions. Compared to immediate implant–based reconstruction, tissue expander–based reconstructions had significantly more minor cellulitis (p = 0.0006) but less complete nipple necrosis (p = 0.0005) and major (p < 0.0001) and minor (p = 0.0028) mastectomy flap necrosis (p = 0.0059). Immediate implant–based reconstructions had significantly more minor cellulitis (p = 0.0051), minor mastectomy flap necrosis (p = 0.0425), and partial nipple necrosis (p = 0.0437) compared with autologous tissue–based reconstructions. Outcomes were otherwise equivalent among the three groups. Conclusions: Tissue expander, immediate implant, and autologous tissue breast reconstruction techniques may all be safely offered with nipple-sparing mastectomy. However, reconstructive complications appear to be greater with immediate implant– and autologous tissue–based techniques compared with tissue expander–based reconstruction.

Is Rotation a Concern with Anatomical Breast Implants? A Statistical Analysis of Factors Predisposing to Rotation

Is Rotation a Concern with Anatomical Breast Implants? A Statistical Analysis of Factors Predisposing to Rotation

Montemurro, P et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1367–1378

Background: Since their introduction in 1993, anatomical implants have provided a more natural appearance in breast augmentation, and many surgeons advocate their use and promote the good aesthetic results. However, the risk of implant rotation makes some of them reluctant to use these devices. The rotation rate varies among authors. 
Methods: The authors present a 6.5-year series of 531 patients who underwent primary breast augmentation with macrotextured anatomical implants in a Swedish facility performed by one consultant surgeon (P.M.). The authors examined the rotation rate and the correlation with possible predisposing factors such as preoperative breast cup size, childbirth, and body mass index. 
Results: A total of 20 implants (1.88 percent; 95 percent CI, 1.15 to 2.89 percent) in 19 patients (3.58 percent; 95 percent CI, 2.17 to 5.53 percent) were rotated. In one patient (0.22 percent), both implants rotated, whereas in the remaining patients, the rotation was unilateral. The authors were unable to establish a statistically significant correlation between implant rotation and previous childbirth or increased body mass index. However, there was a relation between rotation rate and preoperative breast cup size that showed an upward trend as the cup size increased from A to C. 
Conclusion: The authors believe that if the implant is correctly selected and the operation is performed meticulously with proper pocket dissection, the rotation rate is minimal and it should not be considered a disadvantage for the use of anatomical implants.

Should Immediate Autologous Breast Reconstruction Be Considered in Women Who Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes

Should Immediate Autologous Breast Reconstruction Be Considered in Women Who Require Postmastectomy Radiation Therapy? A Prospective Analysis of Outcomes

Billig, J et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1279–1288

Background: In women who require postmastectomy radiation therapy, immediate autologous breast reconstruction is often discouraged. The authors prospectively evaluated postoperative morbidity and satisfaction reported by women undergoing delayed or immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy. 
Methods: Patients enrolled in the Mastectomy Reconstruction Outcomes Consortium study, who received postmastectomy radiotherapy and underwent immediate or delayed free abdominally based autologous breast reconstruction, were identified. Postoperative complications at 1 and 2 years after reconstruction were assessed. Patient-reported outcomes were evaluated using the BREAST-Q questionnaire preoperatively and at 1 and 2 years postoperatively. Bivariate analyses and mixed-effects regression models were used to compare outcomes. 
Results: A total of 175 patients met the authors’ inclusion criteria. Immediate reconstructions were performed in 108 patients and delayed reconstructions in 67 patients; 93.5 percent of immediate reconstructions were performed at a single center. Overall complication rates were similar based on reconstructive timing (25.9 percent immediate and 26.9 percent delayed at 1 year; p = 0.54). Patients with delayed reconstruction reported significantly lower prereconstruction scores (p < 0.0001) for Satisfaction with Breasts and Psychosocial and Sexual Well-being than did patients with immediate reconstruction. At 1 and 2 years postoperatively, both groups reported comparable levels of satisfaction in assessed BREAST-Q domains. 
Conclusions: From this prospective cohort, immediate autologous breast reconstruction in the setting of postmastectomy radiation therapy appears to be a safe option that may be considered in select patients and centers. Breast aesthetics and quality of life, evaluated from the patient’s perspective, were not compromised by flap exposure to radiation therapy. 

Principles of Breast Re-Reduction: A Reappraisal

Principles of Breast Re-Reduction: A Reappraisal

Mistry, RM et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1313–1322

Background: This article examines outcomes following breast re-reduction surgery using a random pattern blood supply to the nipple and vertical scar reduction. Methods: A retrospective review was conducted of patients who underwent bilateral breast re-reduction surgery performed by a single surgeon over a 12-year period. Patient demographics, surgical technique, and outcomes were analyzed. Results: Ninety patients underwent breast re-reduction surgery. The average interval between primary and secondary surgery was 14 years (range, 0 to 42 years). The majority of patients had previously undergone primary breast reduction using an inferior pedicle [n = 37 (41 percent)]. Breast re-reduction surgery was most commonly performed using a random pattern blood supply, rather than recreating the primary pedicle [n = 77 (86 percent)]. The nipple-areola complex was repositioned in 60 percent of patients (n = 54). The mean volume of tissue resected was 250 g (range, 22 to 758 g) from the right breast and 244 g (range, 15 to 705 g) from the left breast. Liposuction was also used adjunctively in all cases (average, 455 cc; range, 50 to 1750 cc). Two patients experienced unilateral minor partial necrosis of the areolar edge but not of the nipple itself (2 percent). Conclusions: Breast re-reduction can be performed safely and predictably, even when the previous technique is not known. Four key principles were developed: (1) the nipple-areola complex can be elevated by deepithelialization rather than recreating or developing a new pedicle; (2) breast tissue is removed where it is in excess, usually inferiorly and laterally; (3) the resection is complemented with liposuction to elevate the bottomed-out inframammary fold; and (4) skin should not be excised horizontally below the inframammary fold. 

Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study

Fat Grafting after Invasive Breast Cancer: A Matched Case-Control Study

Petit, JY et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1292–1296

Background: Fat grafting has been widely indicated for postmastectomy and postlumpectomy breast reconstruction. The literature emphasizes the clinical efficacy of fat grafting, but experimental studies raise important questions about the recurrence risk because of the stimulation of remaining cancer cells by progenitor or adult adipocytes. Because breast conservative treatment provides a higher risk of residual cancer cells in the breast tissue compared with mastectomy, the authors set up a matched case-control study of fat grafting versus no fat grafting after breast conservative treatment. Methods: The authors collected data from 322 consecutive patients operated on for a primary invasive breast cancer who subsequently underwent fat grafting for breast reshaping from 2006 to 2013. All patients were free of recurrence before fat grafting. For each patient, the authors selected one patient with similar characteristics who did not undergo fat grafting. Results: After a mean follow-up of 4.6 years (range, 0.1 to 10.2 years) after fat grafting, or a corresponding time for controls, the authors observed no difference in the incidence of local events (fat grafting, n = 14; controls, n = 16; p = 0.49), axillary nodes metastasis (fat grafting, n = 3; controls, n = 6; p = 0.23), distant metastases (fat grafting, n = 14; controls, n = 15; p = 0.67), or contralateral breast cancer (fat grafting, n = 4; controls, n = 4; p = 0.51). Conclusion: Fat grafting seems to be a safe procedure after breast conservative treatment for breast cancer patients. 

Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy

Breast Cancer after Augmentation: Oncologic and Reconstructive Considerations among Women Undergoing Mastectomy

Cho, E et al
Plastic & Reconstructive Surgery: June 2017 - Volume 139 - Issue 6 - p 1240e–1249e

Background: Breast augmentation with subglandular versus subpectoral implants may differentially impact the early detection of breast cancer and treatment recommendations. The authors assessed the impact of prior augmentation on the diagnosis and management of breast cancer in women undergoing mastectomy. 
Methods: Breast cancer diagnosis and management were retrospectively analyzed in all women with prior augmentation undergoing therapeutic mastectomy at the authors’ institution from 1993 to 2014. Comparison was made to all women with no prior augmentation undergoing mastectomy in 2010. Subanalyses were performed according to prior implant placement. Results: A total of 260 women with (n = 89) and without (n = 171) prior augmentation underwent mastectomy for 95 and 179 breast cancers, respectively. Prior implant placement was subglandular (n = 27) or subpectoral (n = 63) (For five breasts, the placement was unknown). Breast cancer stage at diagnosis (p = 0.19) and detection method (p = 0.48) did not differ for women with and without prior augmentation. Compared to subpectoral augmentation, subglandular augmentation was associated with the diagnosis of invasive breast cancer rather than ductal carcinoma in situ (p = 0.01) and detection by self-palpation rather than screening mammography (p = 0.03). Immediate two-stage implant reconstruction was the preferred reconstructive method in women with augmentation (p < 0.01). 
Conclusions: Breast cancer stage at diagnosis was similar for women with and without prior augmentation. Among women with augmentation, however, subglandular implants were associated with more advanced breast tumors commonly detected on palpation rather than mammography. Increased vigilance in breast cancer screening is recommended among women with subglandular augmentation.