Attualità in Senologia

Rassegna della letteratura: gennaio/marzo 2020
Chirurgia oncologica, chirurgia plastica-ricostruttiva, radioterapia 

The survival benefit of postmastectomy radiotherapy for breast cancer patients with T1-2N1 disease according to molecular subtype.
Wei J, Jiang Y, Shao Z – Breast. 2020 Mar 12;51:40-49.
Background:  To evaluate the significance of postmastectomy radiotherapy (PMRT) in female breast cancer patients with T1-2N1M0 disease according to molecular subtypes and other risk factors
Methods: We conducted a retrospective cohort-based study utilizing the Surveillance, Epidemiology, and End Results database. Patients who were diagnosed with T1-2N1M0 invasive breast cancer and received mastectomy between 2010 and 2014 were enrolled in our study. Overall survival (OS) was calculated with Kaplan-Meier method, and multivariant Cox hazard model was conducted to identify the impact of PMRT according to molecular subtypes and other risk factors. Propensity score matching (PSM) was applied to balance measurable confounders.
Results:  Of all the 16,521 enrolled patients, 5775 (35.0%) cases received PMRT. The distribution of molecular subtype is 71.4% for Luminal A, 13.2% for Luminal B, 5.1% for HER2 enriched, and 10.3% for TNBC. The OS was significantly better for patients in PMRT group than the Non-PMRT group (P < 0.0001). Stratified by molecular subtype, PMRT significantly prolonged survival in Luminal A patients (HR: 0.759, 95% CI: 0.651-0.884, P < 0.001), Yet it brought no significant survival advantage in Luminal B, TNBC or HER2 enriched subtype (P = 0.914, P = 0.124, P = 0.103, respectively). Also, PMRT bore prognostic significance among those patients who were older than 56 years old, single, white, exempt from reconstruction and chemotherapy, and were with ductal, GradeⅡtumor (all P < 0.05). After PSM, the survival benefit of PRMT sustained in Luminal A patients with T1 tumor concomitant with one positive lymph node.
Conclusions:  Our study demonstrates a beneficial impact for PMRT on overall survival among Luminal A subtype breast cancer patients with T1-2N1 disease. The selection of PMRT should be stratified by molecular subtype and other risk factors

Surgical timing following neoadjuvant chemotherapy for breast cancer affects postoperative complication rates.
Sutton TL, Johnson N, Schlitt A et Al. – Am J Surg. 2020 Mar 10.
Background:  Neoadjuvant chemotherapy (NAC) is increasingly used in the treatment of breast cancer. The time interval from last dose of cytotoxic chemotherapy to surgery (TTS) can vary widely. We aimed to evaluate the effect of TTS on postoperative complications.
Methods: A retrospective review for women treated with NAC at our institution between January 2011 through December 2016 was performed. Charts were reviewed for postoperative wound complications, and multivariate analysis was performed
Results:  455 patients were identified. Median TTS was 30 days (range 11-228). On multivariate analysis, TTS of less than 28 days was associated with 70% higher odds of any wound complication (p < 0.05). Increasing age had the strongest association with the presence of any wound complication (p < 0.0001). The majority of complications were treated in the outpatient setting (n = 80, 83%).
Conclusions:  Following NAC for breast cancer, TTS less than 28 days is a risk factor for postoperative wound complications; however, the majority of complications are minor and treated in the outpatient setting. Additional data are needed to determine optimal TTS for oncologic outcomes.

Quality of life after breast-conserving therapy and adjuvant radiotherapy for non-low-risk ductal carcinoma in situ (BIG 3-07/TROG 07.01): 2-year results of a randomised, controlled, phase 3 trial.
King MT, Link EK, Whelan TJ et Al. – Lancet Oncol. 2020 Mar 20.
Background:  BIG 3-07/TROG 07.01 is an international, multicentre, randomised, controlled, phase 3 trial evaluating tumour bed boost and hypofractionation in patients with non-low-risk ductal carcinoma in situ following breast-conserving surgery and whole breast radiotherapy. Here, we report the effects of diagnosis and treatment on health-related quality of life (HRQOL) at 2 years.
Methods: The BIG 3-07/TROG 07.01 trial is ongoing at 118 hospitals in 11 countries. Women aged 18 years or older with completely excised non-low-risk ductal carcinoma in situ were randomly assigned, by use of a minimisation algorithm, to tumour bed boost or no tumour bed boost, following conventional whole breast radiotherapy or hypofractionated whole breast radiotherapy using one of three randomisation categories. Category A was a 4-arm randomisation of tumour bed boost versus no boost following conventional whole breast radiotherapy (50 Gy in 25 fractions over 5 weeks) versus hypofractionated whole breast radiotherapy (42·5 Gy in 16 fractions over 3·5 weeks). Category B was a 2-arm randomisation between tumour bed boost versus no boost following conventional whole breast radiotherapy, and category C was a 2-arm randomisation between tumour bed boost versus no boost following hypofractionated whole breast radiotherapy. Stratification factors were age at diagnosis, planned endocrine therapy, and treating centre. The primary endpoint, time to local recurrence, will be reported when participants have completed 5 years of follow-up. The HRQOL statistical analysis plan prespecified eight aspects of HRQOL, assessed by four questionnaires at baseline, end of treatment, and at 6, 12, and 24 months after radiotherapy: fatigue and physical functioning (EORTC QLQ-C30); cosmetic status, breast-specific symptoms, arm and shoulder functional status (Breast Cancer Treatment Outcome Scale); body image and sexuality (Body Image Scale); and perceived risk of invasive breast cancer (Cancer Worry Scale and a study-specific question). For each of these measures, tumour bed boost was compared with no boost, and conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy, by use of generalised estimating equation models. Analyses were by intention to treat, with Hochberg adjustment for multiple testing. This trial is registered with, NCT00470236.
Results:  Between June 1, 2007, and Aug 14, 2013, 1208 women were enrolled and randomly assigned to receive no tumour bed boost (n=605) or tumour bed boost (n=603). 396 of 1208 women were assigned to category A: conventional whole breast radiotherapy with tumour bed boost (n=100) or no boost (n=98), or to hypofractionated whole breast radiotherapy with tumour bed boost (n=98) or no boost (n=100). 447 were assigned to category B: conventional whole breast radiotherapy with tumour bed boost (n=223) or no boost (n=224). 365 were assigned to category C: hypofractionated whole breast radiotherapy with tumour bed boost (n=182) or no boost (n=183). All patients were followed up at 2 years for the HRQOL analysis. 1098 (91%) of 1208 patients received their allocated treatment, and most completed their scheduled HRQOL assessments (1147 [95%] of 1208 at baseline; 988 [87%] of 1141 at 2 years). Cosmetic status was worse with tumour bed boost than with no boost across all timepoints (difference 0·10 [95% CI 0·05-0·15], global p=0·00014, Hochberg-adjusted p=0·0016); at the end of treatment, the estimated difference between tumour bed boost and no boost was 0·13 (95% CI 0·06-0·20; p=0·00021), persisting at 24 months (0·13 [0·06-0·20]; p=0·00021). Arm and shoulder function was also adversely affected by tumour bed boost across all timepoints (0·08 [95% CI 0·03-0·13], global p=0·0033, Hochberg adjusted p=0·045); the difference between tumour bed boost and no boost at the end of treatment was 0·08 (0·01 to 0·15, p=0·021), and did not persist at 24 months (0·04 [-0·03 to 0·11], p=0·29). None of the other six prespecified aspects of HRQOL differed significantly after adjustment for multiple testing. Conventional whole breast radiotherapy was associated with worse body image than hypofractionated whole breast radiotherapy at the end of treatment (difference -1·10 [95% CI -1·79 to -0·42], p=0·0016). No significant differences were reported in the other PROs between conventional whole breast radiotherapy compared with hypofractionated whole breast radiotherapy.
Conclusions:  Tumour bed boost was associated with persistent adverse effects on cosmetic status and arm and shoulder functional status, which might inform shared decision making while local recurrence analysis is pending.

Volume replacement with diced acellular dermal matrix in oncoplastic breast-conserving surgery: a prospective single-center experience.
Gwak H, Jeon YW, Lim ST et Al. – World J Surg Oncol. 2020 Mar 24;18(1):60
Background:  Several studies have reported the use of acellular dermal matrix in breast reconstruction. However, the primary role of acellular dermal matrix in these studies was to support the implant; there are no reports on the use of acellular dermal matrix exclusively as volume replacement. Thus, we aimed to evaluate the safety and effectiveness of filling of the defect with acellular dermal matrix in oncoplastic breast-conserving surgery.
Methods: We prospectively recruited 120 adult breast cancer patients who were scheduled to undergo oncoplastic breast-conserving surgery with acellular dermal matrix filling from 2017 to 2018. Intraoperatively, diced human acellular dermal matrix measuring 3-5 mm was used on each side to fill in the excisional defect immediately. After 6 months, satisfaction of the patients and surgeons with overall and cosmetic outcomes was evaluated with a survey using a 10-point scale. Postoperative complications were assessed at 2 weeks and 6 months postoperatively.
Results:  Of the 117 patients who were evaluated for their satisfaction, 94.0% were strongly satisfied with the cosmetic outcomes and 90.4% were strongly satisfied overall. Patient overall satisfaction scores were higher than surgeon satisfaction scores (p < 0.001). Of the 117 patients who underwent evaluation of complications 6 months postoperatively, six (5.1%) had hematoma and seven (6.0%) had seroma. The overall reoperation rate due to complications was 8.5%. Only two patients needed acellular dermal matrix removal due to hematoma and inflammation.
Conclusions:  Oncoplastic breast-conserving surgery with acellular dermal matrix filling of defects can be performed safely with high cosmetic satisfaction.

Oncologic Outcomes of Nipple-sparing Mastectomy and Immediate Reconstruction After Neoadjuvant Chemotherapy for Breast Cancer.
Wu ZY, Kim HJ, Lee JW et Al – Ann Surg. 2020 Mar 20.
Background:  To evaluate the oncologic outcomes and risk factors for locoregional recurrence (LRR) and nipple-areola complex recurrence (NR) in a large series of breast cancer patients who underwent nipple-sparing mastectomy (NSM) and immediate reconstruction after neoadjuvant chemotherapy (NACT). The use of NSM and immediate reconstruction in breast cancer patients receiving NACT is increasing. However, the oncologic safety of this approach is unclear
Methods: A total of 310 breast cancer patients (319 breasts) who underwent NACT and NSM between February 2010 and November 2016 were retrospectively analyzed. Clinical and pathologic factors associated with increased risks of LRR and NR were analyzed using univariate (Chi-square or Fisher exact test) and multivariate (Cox proportional hazard regression model) analyses
Results:  During a mean follow-up of 63 ± 22 months, 38 cases had LRR as the first event, including 6 cases of NR as the first event. The 5-year cumulative LRR and NR rates were 11.0% and 1.9%, respectively. In univariate analysis, clinical T stage, pathologic nodal status, histologic grade, lymphovascular invasion, and post-NACT Ki67 status were associated with increased LRR risk, and post-NACT Ki67 status was the only significant risk factor for NR. In multivariate analysis, post-NACT Ki67 ≥10% (hazard ratio, 4.245; 95% confidence interval, 1.865-9.663; P = 0.001) was an independent risk factor for LRR.
Conclusions:  NSM and immediate reconstruction seem to be oncologically safe with acceptable LRR and NR rates for appropriately selected breast cancer patients treated with NACT. Post-NACT Ki67 ≥10% was associated with increased risk of LRR or NR, and therefore, necessitates cautious follow-up.

Outcomes of Sentinel Lymph Node Biopsy Using Blue Dye Method for Early Breast Cancer – A Single-Institution Experience in the Philippines.
Yap RV, De La Serna FM – Breast Cancer (Dove Med Press). 2020 Mar 11;12:37-44.
Background:  This study aimed to share our experience with SLNB in the Filipino population with early breast cancer.
Methods: A retrospective review was done on all patients with confirmed invasive breast carcinoma, tumor size of 5 cm or less (T1/T2), who preoperatively had no clinical signs of axillary metastasis and subsequently underwent SLNB with blue dye method from January 01, 2008 to December 31, 2017. Clinicopathologic profiles were recorded. Outcomes of patients who had SLNB only were assessed.
Results:  One hundred twenty-nine patients matched the inclusion criteria with a mean age of 54.3 years. The majority (88.4%) had a total mastectomy. Invasive ductal carcinoma (65.1%) was the most common tumor. Estrogen and progesterone receptors were positive in 69% and 61.2% respectively while only 28.7% were HER2 positive. SLNB was successfully carried out in 126 (97.7%) patients with a range of 2-4 SLNs harvested. Thirty-four (26.4%) patients had completion ALND. With a median of 25 months follow-up, 75 out of 95 patients who underwent SLNB alone had follow-up data. Forty-six (61.3%) patients had seroma formation. One (1.3%) patient developed arm paresthesia, 2 (2.7%) local (chest wall) and 2 (2.7%) axillary recurrences after a negative SLNB. None of the patients developed lymphedema.
Conclusions:  The blue dye method alone is acceptable and can be readily employed in institutions with limited resources. Even with the limited population, the morbidity and oncologic outcomes of patients who underwent SLNB alone were low and comparable to similar international published data. SLNB should be the preferred method for staging the axilla.

The effect of post mastectomy radiation therapy on survival in breast cancer patients with N1mic disease.
Patel M, Li C, Aronson JH et Al. – Breast. 2020 Mar 6;51:50-56.
Background:  The role of post mastectomy radiation therapy (PMRT) in patients with N1mic breast cancer has not been well defined. A retrospective analysis was performed using the SEER database to evaluate the impact of PMRT on survival in patients with N1mic breast cancer.
Methods: Women with T1-T2, N1mic, M0 breast cancer who had undergone mastectomy were analyzed. Descriptive statistics were calculated for all variables. Univariate analysis to assess for differences in survival with respect to covariates was performed using the log rank test while multivariate analysis was performed with Cox proportional hazards regression. Sub-cohort analysis with propensity score matching was used to assess differences in survival among patients undergoing PMRT vs no PMRT. Comparisons were considered statistically significant at P < 0.05.
Results:  Among 5878 patients, 1202 (20%) underwent PMRT. On univariate analysis, PMRT was a significant predictor of CSS, but not OS. There was no difference in either OS or CSS between the PMRT vs no PMRT groups on multivariate Cox regression analysis and after propensity score matching.
Conclusions:  Among patients with T1-T2, N1mic, M0 breast IDC from the SEER database, there was no difference in either OS or CSS among patients who underwent PMRT vs no PMRT. These results suggest that PMRT does not impact survival among breast cancer patients with N1mic disease. However, additional prospective studies with longer follow up are necessary for further evaluation

Regional nodal irradiation in pT1-2N1 breast cancer patients treated with breast-conserving surgery and whole breast irradiation.
Park SH, Kim JC. – Radiat Oncol J. 2020 Mar;38(1):44-51
Background:  To evaluate the necessity of regional nodal irradiation (RNI) for pT1-2N1 breast cancer patients treated with breast-conserving surgery and radiotherapy, we compared clinical outcomes of patients treated with and without RNI.
Methods: We retrospectively analyzed the data of 214 pT1-2N1 breast cancer patients treated with breast-conserving surgery and whole breast irradiation from 2009-2016. There were 142 (66.4%), 51 (23.85%), and 21 (9.8%) patients with one, two, and three positive lymph nodes, respectively. Thirty-six patients (16.8%) underwent RNI. Adjuvant chemotherapy, endocrine therapy, and anti-HER2 therapy were given to 91.6%, 79.0%, and 15.0% patients, respectively. The most common chemotherapy regimen was anthracycline + cyclophosphamide, followed by taxane (76.5%). The median follow-up was 64 months (range, 6 to 147 months). Patients were propensity matched 1:2 into RNI and no-RNI groups.
Results:  Two patients experienced locoregional recurrences simultaneously with distant metastases, ten patients developed distant metastases, and one patient died. Before matching, the 5-year actuarial locoregional control (LRC), distant metastasis-free survival (DMFS), and overall survival (OS) rates in the RNI and no-RNI groups were 100.0% and 99.4% (p = 0.629), 94.1% and 96.0% (p = 0.676), and 100.0% and 99.4% (p = 0.658), respectively. After matching, the 5-year LRC, DMFS, and OS were 98.3% and 100.0% (p = 0.455), 96.6% and 93.9% (p = 0.557), and 100.0% and 100.0% (p > 0.999) in the RNI and no-RNI groups, respectively. No clinicopathologic or treatment-related factors were significantly associated with LRC, DMFS, or OS.
Conclusions:  Adding RNI did not show superior LRC, DMFS, or OS in pT1-2N1 breast cancer patients.

Breast implant-associated anaplastic large cell lymphoma: emotional impact and guidelines for psychological support.
Oliveri S, Ongaro G, Durosini I – Breast Cancer Res Treat. 2020 Mar 31.
Background:  During the last two decades, the number of breast implants used in aesthetic, oncologic, and risk-reducing surgery has increased substantially mainly due to the improvement and confirmed safety of these devices. Since the identification of the first case of anaplastic large cell lymphoma associated with a breast implant (BIA-ALCL) 20 years ago, there has been an increase in the number of reports of this very rare disease, demonstrating a clear association with breast implants. While the majority of cases are localized and cured by implant removal and full capsulectomy, a small percentage require chemotherapy and the mortality rate is very low. Nevertheless, the evidence linking BIA-ALCL to implant surface texturing has raised concerns about the long-term safety of these devices resulting in patient and regulatory authority concerns globally.
Methods and results:  In this commentary, we report the current debate on BIA-ALCL and the main European government’s actions, with a special focus on the emotional impact that media coverage has on cancer patients. We comment the emotional impact of such risk for patients with breast implant, the hard process of patient’s acceptance for mastectomy and reconstructive surgery, and how this is an essential part of recovery and return to the normal living for many women.
Conclusions:  We conclude by providing guidelines for patient-physician communication and patients’ psychological support on this topic of delicate actuality. Our contribution aims at guiding the medical community in managing risk communication about BIA-ALCL with a multidisciplinary approach, according to the most recently available published evidence.

Ulteriori segnalazioni;

Is it possible to abandon sentinel lymph node biopsy in breast cancer patients withnegative axillary ultrasound in the post-Z0011 era? A retrospective analysis.
Dostalek L, Lednicky S, Saskova P et Al. – Breast J. 2020 Mar 18. doi: 10.1111/tbj.13814

Time to Adjuvant Radiotherapy in Breast Cancer Affects Survival: Implications for the American College of Surgeons Commission on Cancer Quality Metrics.
Zheleva V, Nelson RA, Dumitra S, Vora NL, Lai LL. – Ann Surg Oncol. 2020 Mar 17.

Comparison between sentinel lymph node hybrid scintigraphy and blue dye technique in breast cancer patients: An institutional experience.
Siddique M, Hassan A, Nawaz MK – World J Nucl Med. 2020 Jan 29;19(1):21-27.

A Breast Reconstruction after Mastectomy in Women with Breast Cancer: A Systematic and
Meta-Analysis Review.
Anbiyaiee A, Abouali Galeh Dari – M J Plast Surg. 2020 Jan;9(1):3-9

Management of the axilla following neoadjuvant chemotherapy for breast cancer- A change inpractice.
Riogi B, Sripadam R, Barker D, Harris O et Al – Surgeon. 2020 Mar 16.

Radiofrequency Ablation of the Surgical Bed After Lumpectomy in Breast-conserving Surgery.
Jiménez Mazure C, Ribeiro González M, – Cir Esp. 2020 Mar 16

A Interdisciplinary Treatment of Breast Cancer After Mastectomy With Autologous Breast Reconstruction Using Abdominal Free Flaps in a University Teaching Hospital-A Standardized and Safe Procedure.
Steiner D, Horch RE, Ludolph I et Al – Front Oncol. 2020 Mar 5;10:177.

Contralateral prophylactic mastectomy for unilateral breast cancer in women at average risk: Systematicreview of patient reported outcomes. Psychooncology.
Srethbhakdi A, Brennan ME, Hamid G, Flitcroft K. 2020 Mar 22.

Recent advances in radiotherapy of breast cancer.
Haussmann J, Corradini S, Nestle-Kraemling C – Oncol. 2020 Mar 30;15(1):71

An economic analysis of prophylactic lymphovenous anastomosis among breast cancer patients receiving mastectomy with axillary lymph node dissection.
Squitieri L, Rasmussen PW, Patel KM.  – J Surg Oncol. 2020 Mar 23.

Time to Adjuvant Radiotherapy in Breast Cancer Affects Survival: Implications for the American College of Surgeons Commission on Cancer Quality Metrics.
Zheleva V, Nelson RA, Dumitra S, Vora NL, Lai LL. – Ann Surg Oncol. 2020 Mar 17.