Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer: final 10-year analysis of the open-label, single-arm, phase 2 APT trial

 

The Lancet Oncology:  VOLUME 24, ISSUE 3, P273-285, MARCH 2023

 

Background

We aimed to report on long-term outcomes of patients with small, node-negative, HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab and to establish potential biomarkers to predict prognosis.

Methods

In this open-label, single-arm, phase 2 study, patients aged 18 years or older, with small (≤3 cm), node-negative, HER2-positive breast cancer, and an Eastern Cooperative Oncology Group performance status of 0–1, were recruited from 16 institutions in 13 cities in the USA. Eligible patients were given intravenous paclitaxel (80 mg/m2) with intravenous trastuzumab (loading dose of 4 mg/kg, subsequent doses 2 mg/kg) weekly for 12 weeks, followed by trastuzumab (weekly at 2 mg/kg or once every 3 weeks at 6 mg/kg) for 40 weeks to complete a full year of trastuzumab. The primary endpoint was 3-year invasive disease-free survival. Here, we report 10-year survival outcomes, assessed in all participants who received protocol-defined treatment, with exploratory analyses using the HER2DX genomic tool. This study is registered on ClinicalTrials.gov, NCT00542451, and is closed to accrual.

Findings

Between Oct 29, 2007, and Sept 3, 2010, 410 patients were enrolled and 406 were given adjuvant paclitaxel and trastuzumab and included in the analysis. Mean age at enrolment was 55 years (SD 10·5), 405 (99·8%) of 406 patients were female and one (0·2%) was male, 350 (86·2%) were White, 28 (6·9%) were Black or African American, and 272 (67·0%) had hormone receptor-positive disease. After a median follow-up of 10·8 years (IQR 7·1–11·4), among 406 patients included in the analysis population, we observed 31 invasive disease-free survival events, of which six (19·4%) were locoregional ipsilateral recurrences, nine (29·0%) were new contralateral breast cancers, six (19·4%) were distant recurrences, and ten (32·3%) were all-cause deaths. 10-year invasive disease-free survival was 91·3% (95% CI 88·3–94·4), 10-year recurrence-free interval was 96·3% (95% CI 94·3–98·3), 10-year overall survival was 94·3% (95% CI 91·8–96·8), and 10-year breast cancer-specific survival was 98·8% (95% CI 97·6–100). HER2DX risk score as a continuous variable was significantly associated with invasive disease-free survival (hazard ratio [HR] per 10-unit increment 1·24 [95% CI 1·00–1·52]; p=0·047) and recurrence-free interval (1·45 [1·09–1·93]; p=0·011).

Interpretation

Adjuvant paclitaxel and trastuzumab is a reasonable treatment standard for patients with small, node-negative, HER2-positive breast cancer. The HER2DX genomic tool might help to refine the prognosis for this population.

 

Association of Unilateral Latissimus Dorsi Muscle Harvest for Breast Reconstruction with Postoperative Spinal Posture

 

by Kim, Jisu; Lee, Hojune; Pyon, Jai-Kyong; Mun, Goo-Hyun; Bang, Sa Ik; Jeon, Byung-Joon; Lee, Kyeong-Tae 

 

Plastic and Reconstructive Surgery: September 2022 - Volume 150 - Issue 3 - p 644e-654e

 

Background: 

The latissimus dorsi muscle originates from the lower thoracic spine with broad attachment and plays a subsidiary role in spinal postural stability. The authors investigated whether harvesting unilateral latissimus dorsi muscle for breast reconstruction could influence spinal posture in the long term.

Methods: 

Patients who underwent immediate unilateral breast reconstruction between 2002 and 2010 were reviewed. They were grouped according to reconstruction methods: latissimus dorsi muscle flap and tissue expander/implant. The Cobb angle was assessed twice at each of five different time points (preoperatively and 2, 4, 6, and 8 years postoperatively) by an independent physician blinded to the reconstruction modality. Postoperative scoliosis was defined as a mean Cobb angle greater than 10 degrees at 8 years postoperatively. The trends of changes in Cobb angle over time and the rates of postoperative scoliosis were compared between reconstruction methods.

Results: 

In total, 153 women were analyzed, including 102 using latissimus dorsi muscle flap and 51 using tissue expander/implant, with a median follow-up of 103 months. The latissimus dorsi flap group showed enhanced trends of increasing postoperative Cobb angles as compared with the tissue expander/implant group, and the difference remained significant after adjusting for other variables (p = 0.001). The rate of postoperative scoliosis was significantly higher in the latissimus dorsi flap group than in the control group (p = 0.029). Multivariable analyses revealed that use of the latissimus dorsi flap was associated with a significantly increased rate of postoperative scoliosis.

Conclusion: 

Unilateral latissimus dorsi muscle flap harvest for breast reconstruction might be associated with changes in spinal posture in the long term.

 

 

Transverse Upper Gracilis Flap Breast Reconstruction: A 5-Year Consecutive Case Series of Patient-Reported Outcomes

 

by Jessica, Anne Savage; Zhao, Jade; Mackey, Simon; Blackburn, Adam Victor 

 

Plastic and Reconstructive Surgery: August 2022 - Volume 150 - Issue 2 - p 258-268

 

Background: 

The transverse upper gracilis flap is an important reconstructive option for patients who desire autologous reconstruction after mastectomy but in whom a deep inferior epigastric perforator flap is unavailable or undesirable. The authors present an analysis of outcomes and patient satisfaction results, from a consecutive series in a single institution.

Methods: 

Using a prospectively populated free flap database, all patients undergoing transverse upper gracilis flap breast reconstruction for a mastectomy defect between January of 2013 and December of 2017 were identified. Retrospective review of clinical notes, admissions, and discharge information was conducted to identify outcomes, secondary operations, and complications. All patients were contacted by letter and invited to take part in a patient satisfaction survey a minimum of 12 months after free-flap surgery.

Results: 

Seventy-eight patients underwent transverse upper gracilis flap breast reconstruction using a total of 103 transverse upper gracilis flaps to reconstruct 99 breast mounds in the 5-year period studied. Patient satisfaction is evidenced by BREAST-Q scores showing 81 ± 19 percent Satisfaction with Breasts, 80 ± 20 percent Psychosocial Well-Being, and 84 ± 19 percent Physical Well-Being of the chest. Forty-six of 53 (87 percent) report satisfaction with the postoperative appearance of their thigh unclothed and 51 of 53 (96 percent) report satisfaction clothed.

Conclusions: 

This is the first consecutive series of transverse upper gracilis flap breast reconstruction outcomes that presents BREAST-Q scores for multiple, postoperative reconstruction modules and details complications stratified by Clavien-Dindo score. The methodology can be easily replicated and benchmarked against. Our donor-site complication rates are lower than previous publications and patient satisfaction data reveal that this is a well-accepted option for patients.

 

 

 

 

Nerve Blocks in Breast Plastic Surgery: Outcomes, Complications, and Comparative Efficacy

 

by Abi-Rafeh, Jad; Safran, Tyler; Abi-Jaoude, Joanne; Kazan, Roy; Alabdulkarim, Abdulaziz; Davison, Peter G. 

Plastic and Reconstructive Surgery: July 2022 - Volume 150 - Issue 1 - p 1e-12e

Background:

As plastic surgeons continue to evaluate the utility of nonopioid analgesic alternatives, nerve block use in breast plastic surgery remains limited and unstandardized, with no syntheses of the available evidence to guide consensus on optimal approach.

Methods:

A systematic review was performed to evaluate the role of pectoralis nerve blocks, paravertebral nerve blocks, transversus abdominus plane blocks, and intercostal nerve blocks in flap-based breast reconstruction, prosthetic-based reconstruction, and aesthetic breast plastic surgery, independently.

Results:

Thirty-one articles reporting on a total of 2820 patients were included in the final analysis; 1500 patients (53 percent) received nerve blocks, and 1320 (47 percent) served as controls. Outcomes and complications were stratified according to procedures performed, blocks employed, techniques of administration, and anesthetic agents used. Overall, statistically significant reductions in opioid consumption were reported in 91 percent of studies evaluated, postoperative pain in 68 percent, postanesthesia care unit stay in 67 percent, postoperative nausea and vomiting in 53 percent, and duration of hospitalization in 50 percent. Nerve blocks did not significantly alter surgery and/or anesthesia time in 83 percent of studies assessed, whereas the overall, pooled complication rate was 1.6 percent.

Conclusions:

Transversus abdominus plane blocks provided excellent outcomes in autologous breast reconstruction, whereas both paravertebral nerve blocks and pectoralis nerve blocks demonstrated notable efficacy and versatility in an array of reconstructive and aesthetic procedures. Ultrasound guidance may minimize block-related complications, whereas the efficacy of adjunctive postoperative infusions was proven to be limited. As newer anesthetic agents and adjuvants continue to emerge, nerve blocks are set to represent essential components of the multimodal analgesic approach in breast plastic surgery.

 

Breast Surgery Bulletin - May 2022

 

Effective Treatment of Chronic Mastectomy Pain with Intercostal Sensory Neurectomy

 

by Hart, Sarah E.; Agarwal, Shailesh; Hamill, Jennifer B.; Brown, David L.

 

Plastic and Reconstructive Surgery: May 2022 - Volume 149 - Issue 5 - p 876e-880e

 

Chronic postmastectomy pain affects up to 40 percent of patients and leads to diminished quality of life and increased risk of opioid dependence. The cause of this pain is incompletely understood; however, one hypothesis is that direct injury to cutaneous intercostal nerves at the time of mastectomy and/or reconstruction leads to chronic pain. As a result, proximal neurectomy of the involved sensory nerve(s) has been suggested to be effective for these patients. The purpose of this study was to determine whether chronic pain in postmastectomy patients can be diagnosed reliably in an office setting and pain reduced by intercostal sensory neurectomy. The authors performed a retrospective review of seven patients with a history of breast surgery and chronic pain who underwent intercostal neurectomy combined with muscle or dermal wrapping of the proximal end of the resected nerve. All patients were diagnosed by history and physical examination, and suspected nerves were further identified with local anesthetic nerve blocks. An average of 3.14 neurectomies were performed per patient (range, one to six). There was a significant reduction in visual analogue scale pain scores following surgery, from 9 preoperatively to 1 postoperatively (p = 0.02). Eighty-six percent of patients were pain-free or “considerably improved” at their latest follow-up appointment (average, 6.14 months). It is concluded that intercostal sensory nerve injury at the time of mastectomy and/or reconstruction can lead to chronic mastectomy pain, which can be easily diagnosed and effectively treated with intercostal neurectomy. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

 

Impact of Chemotherapy and Radiation Therapy on Inflammatory Response, Neovascularization, and Capsule Formation of Acellular Dermal Matrix in Breast Reconstruction: Analysis of the BREASTrial Biopsy Specimens

 

by Mendenhall, Shaun D.; Graham, Emily M.; Anderson, Layla A.; Ying, Jian; Liu, Ting; Agarwal, Jayant P. 

 

Plastic and Reconstructive Surgery: March 2022 - Volume 149 - Issue 3 - p 378e-385e

 

Background: 

The Breast Reconstruction Evaluation of Acellular Dermal Matrix as a Sling Trial is a single-center, blinded, prospective, randomized, controlled trial established to compare outcomes using two popular types of acellular dermal matrices, AlloDerm and DermaMatrix, in tissue expander breast reconstruction. This study used the acellular dermal matrix biopsy specimens from the trial to evaluate how adjuvant therapy influences inflammation, neovascularization, and capsule formation of the acellular dermal matrix.

Methods: 

Punch biopsy specimens were taken at the time of expander exchange and were analyzed by a blinded pathologist. The inflammatory response was quantified by the number of fibroblasts, giant cells, and lymphocytes. Neovascularization and capsule formation were similarly quantified by the number of new capillaries and capsule presence and thickness, respectively.

Results: 

Histology specimens were collected from 109 patients (170 breasts). In the absence of adjuvant therapy, there was no significant difference between AlloDerm and DermaMatrix in terms of inflammation, neovascularization, or capsule thickness. Both acellular dermal matrices showed a significant decrease in inflammation and neovascularization with adjuvant therapy. When chemotherapy and radiation therapy were used, the decrease in inflammation was greatest for the group reconstructed with DermaMatrix (p < 0.039).

Conclusions: 

Adjuvant therapy influences the inflammatory response, neovascularization, and capsule formation in both acellular dermal matrices. Adjuvant therapy has a protective effect on the inflammatory response toward both acellular dermal matrices in breast reconstruction. In the setting of chemotherapy and radiation therapy, DermaMatrix produced the greatest reduction in inflammation.