The prognostic significance of skin involvement in breast cancer patients with chest wall recurrence.

PURPOSE: To assess the prognostic significance of skin involvement in breast cancer patients with chest wall recurrence (CWR). METHODS: We retrospectively analyzed the clinicopathological data of breast cancer patients with CWR who were diagnosed pathologically between January 2000 and April 2020. Disease-free survival (DFS) was the time from radical resection for CWR to disease recurrence. Progression-free survival (PFS) was defined as the time from the diagnosis of locally unresectable CWR to the first sign of disease progression. Persistent chest wall progression was defined as three consecutive chest wall progressions with no distant organ involvement. RESULTS: A total of 476 patients with CWR were included in this study. Skin involvement was confirmed in 345 patients. Skin involvement was significantly correlated with a high T stage (p = 0.003), more positive nodes at initial examination (p < 0.001) and lymphovascular invasion (p < 0.001). Kaplan-Meier analysis showed that skin involvement was a predictor of shorter DFS (p < 0.001), including both local disease progression (p < 0.001) and distant disease progression (p = 0.022). Multivariate analysis showed that skin involvement was an independent biomarker for DFS (p = 0.043). Patients with skin involvement were more likely to experience persistent chest wall progression (p = 0.040). After eliminating the potential deviation caused by an insufficient follow-up time, persistent chest wall progression was more likely to be associated with a high N stage (p = 0.002), negative progesterone receptor (PR; p = 0.001) and positive human epidermal growth factor receptor 2 (HER2; p = 0.046) of the primary site, and negative oestrogen receptor (ER; p = 0.027) and PR (p = 0.013) of the chest wall lesion and skin involvement (p = 0.020). CONCLUSION: Skin involvement was a predictor of poor disease control in patients with CWR and was closely related to persistent chest wall progression. We stratified the prognosis of individualized treatment for breast cancer patients with CWR to provide new insights into the biological behaviours of the disease.

Skin involvement is a predictor of poor local disease control in breast cancer patients with CWR and a factor contributing to persistent chest wall progression after CWR. We stratified the prognosis of individualized treatment for breast cancer patients with CWR.

A prediction model for distant metastasis after isolated locoregional recurrence of breast cancer.

PURPOSE: The impact of progesterone receptor (PR) status on the prognosis of breast cancer after isolated locoregional recurrence (ILRR) remains unclear. This study evaluated the impact of clinicopathologic factors, including PR status of ILRR, on distant metastasis (DM) after ILRR. METHODS: We retrospectively identified 306 patients with ILRR diagnosed at the National Cancer Center Hospital between 1993 and 2021 from the database. Cox proportional hazards analysis was performed to examine factors associated with DM after ILRR. We developed a risk prediction model based on the number of detected risk factors and estimated survival curves using the Kaplan-Meier method. RESULTS: During a median follow-up time of 4.7 years after ILRR diagnosis, 86 patients developed DM, and 50 died. Multivariate analysis revealed that seven risk factors were associated with poor distant metastasis-free survival (DMFS): estrogen receptor-positive/PR-negative/human epidermal growth factor receptor 2-negative ILRR, short disease-free interval, recurrence site other than ipsilateral breast, no-resection of ILRR tumor, chemotherapy for the primary tumor, nodal stage in the primary tumor, and no endocrine therapy for ILRR. The predictive model classified patients into 4 groups based on the number of risk factors: low-, intermediate-, high-, and the highest-risk groups with 0 to 1, 2, 3 to 4, and 5 to 7 factors, respectively. This revealed significant variation in DMFS among the groups. A higher number of the risk factors was associated with poorer DMFS. CONCLUSION: Our prediction model, which considered the ILRR receptor status, may contribute to the development of a treatment strategy for ILRR.

Salvage Perioperative Interstitial High-Dose-Rate Interventional Radiotherapy (Brachytherapy) for Local Recurrences of the Chest Wall Following Mastectomy and Previous External Irradiation.

(1) Background: To investigate the technical feasibility, safety, and efficacy of interstitial perioperative high-dose-rate interventional radiotherapy (HDR-IRT, brachytherapy) as a local salvage treatment combined with surgery for local chest wall recurrences following mastectomy and subsequent external beam radiation treatment (EBRT). (2) Methods: A retrospective analysis of 56 patients treated with interstitial HDR-IRT in combination with local surgery of a chest wall recurrence of breast cancer after previous treatment with mastectomy and EBRT from 2008 to 2020. (3) Results: Local recurrence following HDR-IRT was encountered in seven (12.5%) patients. The 1-year local recurrence-free survival (RFS), 3-year RFS, and 5-year RFS were 91%, 82%, and 82%, respectively. The 1-year overall survival (OS), 3-year OS, and 5-year OS was 85.5%, 58%, and 30%, respectively. Acute grade 1-2 radiation dermatitis was observed in 22 (39.3%) patients. Late ≥grade 3 toxicities were encountered in five (8.9%) patients. (4) Conclusions: Salvage perioperative interstitial high-dose-rate interventional radiotherapy (brachytherapy) combined with surgery seems to be an effective interdisciplinary management with acceptable treatment-related toxicity for local recurrences of the chest wall following mastectomy and previous external irradiation.

Surgical reduction in chest wall disease to prolong survival in breast cancer patients: a retrospective study.

Background: Patients with breast cancer (BC) may develop locoregional recurrence alone or with distant metastases. Results of previous studies discussing the benefit of local surgery among patients with chest wall disease were controversial. Whether surgical reduction for chest wall disease could influence survival outcome is still a question. The objective of this study was to compare overall survival (OS) in patients with recurrence involving the chest wall who did or did not undergo surgical reduction after previous treatment of the primary BC to explore the role of surgical reduction. Methods: We retrospectively reviewed BC patients with chest wall as the first recurrent/metastatic site selected between January 2012 and December 2018 to explore whether surgical reduction for chest wall disease could influence OS. Clinicopathological data, including age at initial diagnosis, TNM stage, the pathological parameters, and treatment were recorded and analyzed. OS was primarily described using the Kaplan-Meier estimator for each group, with the statistical significance between groups being tested by the log-rank test. Results: A total of 198 patients with a median age of 48 years (range, 22-73 years) were analyzed. Chest wall as the only site of recurrence occurred in 139 patients (70.2%), and the other 59 (29.8%) patients had other metastatic sites. There were 88 patients who underwent surgical reduction for chest wall recurrence. The median OS was significantly longer for the patients who had chest wall disease reduction than for those who did not {194.2 months [95% confidence interval (CI): 140.4-247.9 months] vs. 102.7 months (95% CI: 79.7-125.7 months), respectively, P=0.001}. From multivariate analysis, surgical reduction was an independent factor significantly influenced OS (HR =0.52, 95% CI: 0.33-0.81, P=0.004). Subgroup analyses showed that OS was statistically longer in the chest wall disease surgical reduction group than in the no reduction group with respect to hormone receptor (HR) negative (-), human epidermal growth factor receptor 2 (HER2) negative (-), triple-negative breast cancer (TNBC), disease-free survival (DFS) >24 months, and chest wall disease only. Conclusions: BC patients with chest wall recurrence could benefit from surgical reduction with a prolonged OS. In a certain selected group, surgical reduction may be warranted.

Radiotherapy for and prognosis of breast cancer patients with isolated chest wall recurrence after mastectomy / 中华放射肿瘤学杂志

Objective:To investigate the radiation field and dose selection of patients with isolated chest wall recurrence (ICWR) after modified radical mastectomy, and analyze the prognostic factors related to subsequent chest wall recurrence.Methods:Clinical data of 201 patients with ICWR after mastectomy admitted to the Fifth Medical Center, Chinese PLA General Hospital from 1998 to 2018 were retrospectively analyzed. None of the patients received postoperative adjuvant radiotherapy. After ICWR, 48 patients (73.6%) underwent surgery and 155 patients (77.1%) received radiotherapy. Kaplan-Meier method was used to calculate the post-recurrence progression-free survival (PFS) rates and the difference was compared by log-rank test. Multivariate analysis was performed using Cox regression model. Competing risk model was adopted to estimate the subsequent local recurrence (sLR) rates after ICWR and the difference was compared with Gray test. Multivariate analysis was conducted using F&G analysis. Results:With a median follow up of 92.8 months after ICWR, the 5-year PFS rate was 23.2%, and the 5-year sLR rate was 35.7%. Multivariate analysis showed that patients with surgery plus radiotherapy and recurrence interval o F>12 months had a lower sLR rate. Patients with recurrence interval o F>48 months, local plus systemic treatment and surgery plus radiotherapy had a higher PFS rate. Among the 155 patients who received chest wall radiotherapy after ICWR, total chest wall irradiation plus local boost could improve the 5-year PFS rate compared with total chest wall irradiation alone (34.0% vs. 15.4%, P=0.004). Chest wall radiation dose (≤60 Gy vs.>60 Gy) exerted no significant effect upon the sLR and PFS rates (both P>0.05). In the 53 patients without surgery, the 5-year PFS rates were 9.1% and 20.5%( P=0.061) with tumor bed dose ≤60 Gy and>60 Gy, respectively. Conclusions:Local radiotherapy is recommended for patients with ICWR after modified radical mastectomy of breast cancer, including total chest wall radiation plus local boost. The radiation dose for recurrence should be increased to 60 Gy, and it should be above 60 Gy for those who have not undergone surgical resection. In addition, patients with ICWR still have a high risk of sLR, and more effective treatments need to be explored.

Patterns of Chest Wall Recurrence and Suggestions on the Clinical Target Volume of Breast Cancer: A Retrospective Analysis of 121 Postmastectomy Patients.

PURPOSE: Radiotherapy is a powerful strategy to prevent chest wall recurrence (CWR) of postmastectomy breast cancer (BC). This retrospective study aims at analyzing patterns of CWR to explore the delineation of clinical target volume. PATIENTS AND METHODS: Detailed clinicopathological information of postmastectomy BC patients with CWR was collected from our single cancer center based on clear criteria. To describe recurrent positions more accurately, the chest wall was divided into three layers: skin layer (skin and subcutaneous tissues), pectoralis layer (pectoralis major and minor), and rib layer (rib and intercostal muscle). The frequency distribution of recurrence location and its association with clinical pathological factors were analyzed. RESULTS: A total of 121 postmastectomy BC with CWR were included in this study. The percentages of breast tumor located in the upper outer quadrant, upper inner quadrant, lower inner quadrant, lower outer quadrant, overlapping quadrant, and areola area were 31.0% (35/113), 26.5% (30/113), 12.4% (14/113), 5.3% (6/113), 21.1% (25/113), and 2.7% (3/113), respectively. HER2-positive BC (51/113, 45.1%) is the most common BC subtype. Analysis on the patterns of CWR showed that recurrences locating in the skin layer, pectoralis layer, rib layer, mixed layers, and incision periphery accounted for 58.6% (68/116), 9.5% (11/116), 1.7% (2/116), 30.2% (35/116), and 60.5% (46/76), respectively. Rates of recurrences located in the skin and/or pectoralis layers for all BC patients, patients with concomitant distance metastasis, and patients without concomitant distance metastasis were 82.8% (96/116), 85.9% (49/57), and 81.0% (47/58), respectively. CONCLUSION: For BC patients receiving mastectomy, skin, subcutaneous tissues, pectoralis, and area around incision have a high risk of recurrence, which should be paid more attention in chest wall radiotherapy.

Prognosis and Prophylactic Regional Nodal Irradiation in Breast Cancer Patients With the First Isolated Chest Wall Recurrence After Mastectomy.

BACKGROUND AND PURPOSE: Optimal radiation target volumes for breast cancer patients with their first isolated chest wall recurrence (ICWR) after mastectomy are controversial. We aimed to analyze the regional failure patterns and to investigate the role of prophylactic regional nodal irradiation (RNI) for ICWR. MATERIALS AND METHODS: Altogether 205 patients with ICWR after mastectomy were retrospectively analyzed. Post-recurrence progression-free survival (PFS) and overall survival (OS) rates were calculated by Kaplan-Meier method and the differences were compared with Log-rank test. Competing risk model was used to estimate the subsequent regional recurrence (sRR) and locoregional recurrence (sLRR) rates, and the differences were compared with Gray test. RESULTS: The 5-year sRR rate was 25.2% with median follow-up of 88.6 months. Of the 52 patients with sRR, 30 (57.7%) recurred in the axilla, 29 (55.8%) in supraclavicular fossa (SC), and five (9.6%) in internal mammary nodes. Surgery plus radiotherapy was independently associated with better sLRR and PFS rates (p<0.001). The ICWR interval of ≤ 4 years was associated with unfavorable sRR (p=0.062), sLRR (p=0.014), PFS (p=0.001), and OS (p=0.005). Among the 157 patients who received radiotherapy after ICWR, chest wall plus RNI significantly improved PFS (p=0.004) and OS (p=0.021) compared with chest wall irradiation alone. In the 166 patients whose ICWR interval was ≤ 4 years, chest wall plus RNI provided the best PFS (p<0.001) and OS (p=0.022) compared with chest wall irradiation alone or no radiotherapy. CONCLUSION: Patients with ICWR have a high-risk of sRR in SC and axilla. Chest wall plus RNI is recommended.

Clinical and dosimetric evaluation of recurrent breast cancer patients treated with hyperthermia and radiation.

Background: Treatment for locally recurrent breast cancer poses a significant challenge because the benefits in local control must be weighed against the increased risk of side effects of the treatment. Frequently, patients have been heavily pre-treated with radiation and several types of chemotherapy. Moreover, they often present with large volumes of bulky disease, further complicating management. Hyperthermia can be used to improve the efficacy of radiation, particularly in the setting of recurrent disease. Methods: We reviewed our clinical and dosimetric experience of breast cancer patients who received hyperthermia and radiation for recurrent breast cancer from 2011 to 2017. Thirty-six patients were treated with hyperthermia and radiation. Median follow-up was 11 months. Thirty patients (83.3%) received prior radiotherapy. The most commonly used radiation fraction scheme was 32 Gy in 8 fractions. The median radiation dose at the time of recurrence was 35.5 Gy (range 20-64 Gy). Mild temperature hyperthermia was delivered two times per week. Results: The median repeat radiation volume was 574 cc (range 11-3620 cc). Electrons, conventional photons, and IMRT radiation techniques were used. IMRT was used for large and complex treatment volumes and showed acceptable doses to organs at risk. The overall response rate was 61.1%. Complete response was observed in 17 patients (47.2%), partial response in 5 patients (13.9%), stable disease in 11 patients (30.6%), and progressive disease in 3 patients (8.3%). Twenty-six patients experienced acute grade 1 and 2 toxicities, primarily pain and erythema; and 26 experienced long-term grade 1 and 2 toxicities, mainly hyperpigmentation and lymphedema. Three patients developed new ulcerations that healed with conservative management. One patient developed pulmonary fibrosis resulting in mild dyspnea on exertion. Conclusion: Hyperthermia and radiation provide good local control with a favorable side effect profile. Thermoradiotherapy may be offered to patients with recurrent breast cancer, including those with extensive volumes of disease.

Reirradiation of recurrent breast cancer with proton beam therapy: A case report and literature review.

BACKGROUND: Locoregional recurrence of breast cancer is challenging for clinicians, due to the various former treatments patients have undergone. However, treatment of the recurrence with systemic therapy and subsequent reirradiation of chest wall is accompanied by increased toxicities, particularly radiation-induced cardiovascular disease. Reirradiation by proton beam therapy (PBT) enables superior preservation of adjacent organs at risk as well as concurrent dose escalation for delivery to the gross tumor. This technology is expected to improve the overall outcome of recurrent breast cancer. CASE SUMMARY: A 47-year-old female presented with an extensive locoregional recurrence at 10 yr after primary treatment of a luminal A breast cancer. Because of tumor progression despite having undergone bilateral ovarectomy and systemic therapy, the patient was treated with PBT total dose of 64.40 Gy to each gross tumor and 56.00 Gy to the upper mediastinal and retrosternal lymphatics including the entire sternum in 28 fractions. Follow-up computed tomography showed a partial remission, without evidence of newly emerging metastasis. At 19 mo after the PBT, the patient developed a radiation-induced pericardial disease and pleural effusions with clinical burden of dyspnea, which were successfully treated by drainage and corticosteroid. Cytological analysis of the puncture fluid showed no malignancy, and the subsequent computed tomography scan indicated stable disease as well as significantly decreased pericardial and pleural effusions. The patient remains free of progression to date. CONCLUSION: PBT was a safe and effective method of reirradiation for locoregionally recurrent breast cancer in our patient.

Chest wall recurrence in pT1-2N0-1 breast cancer patients after mastectomy without radiotherapy.

PURPOSE: In correlation with the nodal status in the era of modern radiotherapy, the chest wall recurrence (CWR) rate was investigated in pT1-2N0-1 breast cancer patients after a mastectomy without post-mastectomy radiotherapy (PMRT). METHODS: The data from the patients participating in two South Korean multi-institutional studies (KROG 14-22; N = 1842 and KROG 14-23; N = 1382) were analyzed. In total, 3224 pT1-2N0-1 breast cancer patients who underwent mastectomy without PMRT were analyzed. RESULTS: The median follow-up time was 72.2 months (range 0.8-125.2 months). The overall CWRs during the follow-up period were 1.68% in N0 patients and 2.82% in N1 patients. There was no statistically significant difference in 5-year and 10-year CWR-free survival (CWRFS) between the N0 and N1 patients. Of the 70 patients with CWR, 33 (1% of all the patients) had isolated CWR, and the 10-year overall survival rate in this group was 96.9%. After the propensity score matching of the N0 and N1 groups, there was still no difference in CWRFS by nodal status. CONCLUSIONS: The incidence of CWR in pT1-2N0-1 breast cancer patients is very low, especially with isolated recurrence. Also, the obtained data showed that the nodal status had no impact on CWRFS.

Re-irradiation and Hyperthermia in Breast Cancer.

Half of locoregional recurrences after breast cancer treatment are isolated events. Restaging should be carried out to select patients for curative salvage treatment. The approach depends on the characteristics of the primary and recurrent cancer, previous locoregional and systemic treatments, site of recurrence, comorbidities and the patient's wishes. A multidisciplinary discussion should be associated with the shared decision-making process. In view of the potential long-term disease-free survival, meticulous target volume delineation and selection of the most appropriate techniques should be used to decrease the risk of toxicity. This overview aims to provide clinicians with tools to manage the different scenarios of breast cancer patients with locoregional recurrences in the context of re-irradiation.

Dramatic Response of an Aggressive Chest Wall Recurrence to Hyperthermia, Radiation, and Chemotherapy.

Hyperthermia has been demonstrated to be an effective adjuvant oncological treatment modality in combination with chemotherapy and/or radiation. Published data have demonstrated that the addition of hyperthermia can improve local control for breast cancer chest wall recurrences. We present a patient with a very aggressive estrogen receptor-negative, progesterone receptor-negative, HER2/neu receptor-negative chest wall recurrence status-post a right modified radical mastectomy. Despite having metastatic disease, in an attempt to achieve local control and provide palliation, she was treated with hyperthermia, radiation, and chemotherapy. A near complete resolution of her chest wall recurrence in a very short time period was seen with a significant improvement in her symptoms. While she unfortunately succumbed to her disease shortly thereafter, the local control that our treatment offered her allowed her quality of life to improve significantly near the end of her life.

Management of Isolated Locoregional Recurrences in Breast Cancer: A Review of Local and Systemic Modalities.

Locoregional recurrence (LRR) after adequate treatment of primary breast cancer poses a therapeutic challenge. Advances in the management of breast cancer have led to significant improvements in survival. With this advantage, it is observed that the incidence of LRR has relatively decreased. Systemic involvement should be ruled out in patients presenting with locoregionally recurrent disease, as isolated LRR requires a treatment with curative intent. Salvage mastectomy following ipsilateral breast tumor recurrence is a time-tested treatment option and widely accepted. Second-time breast conservation surgery with or without radiotherapy is an emerging alternative. Following a second breast conservation, partial breast irradiation has been seen to improve local control. Five-year overall survival with second breast conservation and radiotherapy is in the range of 76% to 100% with acceptable toxicities. Isolated chest wall recurrences after mastectomy are difficult to manage. Multimodality treatment has been adopted to treat chest wall recurrences, following which the 5-year overall survival was observed to be in the range of 45% to 60%. Use of hyperthermia and photodynamic therapy in combination with conventional treatment options has been associated with better clinical outcomes. Systemic therapy, in the form of chemotherapy and/or hormonal therapy in addition to adequate locoregional treatment, has shown to improve survival. Multimodality treatment for isolated regional recurrences has been associated with better outcomes, and the 5-year survival rates are around 50%. All patients with LRR should be evaluated by a multi-disciplinary tumor board to individualize treatment based on the expected risk-benefit ratio of retreatment.

Electrochemotherapy in the Treatment of Massive, Multisite Breast Cancer Metastasis to the Skin and Subcutaneous Tissue: A Case Report.

BACKGROUND: Chest wall recurrence (CWR) from breast cancer after mastectomy is a difficult to treat disease. Electrochemotherapy (ECT) provides a safe, efficient, and non-invasive locoregional treatment approach in this setting. CASE REPORT: A 61-year-old woman presented with unresectable breast cancer recurrence to the skin and subcutaneous tissue for which numerous lines of treatment were unsuccessful. Between February 2015 and May 2015, the patient underwent 3 courses of ECT after which a spectacular regression of the cutaneous metastatic foci was observed. After an overall observation period of 12 weeks, complete clinical remission was achieved. CONCLUSION: ECT can be proposed as an effective and safe locoregional therapy for breast cancer CWR and provides an alternative treatment modality to conventional therapies, especially in the case of multiple cutaneous and subcutaneous lesions.

DEGRO practical guidelines for radiotherapy of breast cancer VI: therapy of locoregional breast cancer recurrences.

OBJECTIVE: To update the practical guidelines for radiotherapy of patients with locoregional breast cancer recurrences based on the current German interdisciplinary S3 guidelines 2012. METHODS: A comprehensive survey of the literature using the search phrases "locoregional breast cancer recurrence", "chest wall recurrence", "local recurrence", "regional recurrence", and "breast cancer" was performed, using the limits "clinical trials", "randomized trials", "meta-analysis", "systematic review", and "guidelines". CONCLUSIONS: Patients with isolated in-breast or regional breast cancer recurrences should be treated with curative intent. Mastectomy is the standard of care for patients with ipsilateral breast tumor recurrence. In a subset of patients, a second breast conservation followed by partial breast irradiation (PBI) is an appropriate alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory. The largest reirradiation experience base exists for multicatheter brachytherapy; however, prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. Following primary mastectomy, patients with resectable locoregional breast cancer recurrences should receive multimodality therapy including systemic therapy, surgery, and radiation +/- hyperthermia. This approach results in high local control rates and long-term survival is achieved in a subset of patients. In radiation-naive patients with unresectable locoregional recurrences, radiation therapy is mandatory. In previously irradiated patients with a high risk of a second local recurrence after surgical resection or in patients with unresectable recurrences, reirradiation should be strongly considered. Indication and dose concepts depend on the time interval to first radiotherapy, presence of late radiation effects, and concurrent or sequential systemic treatment. Combination with hyperthermia can further improve tumor control. In patients with isolated axillary or supraclavicular recurrence, durable disease control is best achieved with multimodality therapy including surgery and radiotherapy. Radiation therapy significantly improves local control and should be applied whenever feasible.

Current Treatment of Isolated Locoregional Breast Cancer Recurrences.

Patients with isolated locoregional breast cancer recurrences should be treated with curative intent. Mastectomy is regarded as the standard of care for patients with ipsilateral breast tumor recurrence. In a selected group of patients, partial breast irradiation after second breast-conserving surgery is a viable alternative to mastectomy. If a second breast conservation is performed, additional irradiation should be mandatory, especially in patients who had not been irradiated previously. In case of re-irradiation, the largest experience exists for multi-catheter brachytherapy. Prospective clinical trials are needed to clearly define selection criteria, long-term local control, and toxicity. In patients with resectable locoregional breast cancer recurrences after mastectomy, multi-modal therapy comprising complete resection, radiation therapy in previously unirradiated patients, and systemic therapy results in 5-year disease-free and overall survival rates of 69% and 88%, respectively. In radiation-naive patients with unresectable, isolated locoregional recurrences, radiation therapy is mandatory. In selected patients with previous irradiations and unresectable locoregional recurrences, a second irradiation as part of an individual treatment concept can be applied. The increased risk of severe toxicity should always be weighed up against the potential clinical benefit. A combination therapy with hyperthermia can further improve the treatment results.

The locoregional recurrence post-mastectomy for ductal carcinoma in situ: Incidence and risk factors.

BACKGROUND: The objective of this retrospective study was to determine the incidence of recurrence of breast cancer after mastectomy for ductal carcinoma in situ (DCIS) in our institution, and to evaluate the associated risk factors while comparing them to those proposed in the literature. METHODS: The files of 218 patients who had undergone mastectomy for pure DCIS or DCIS with micro-invasion at Centre Eugène Marquis between January 2003 and November 2013 were compared for: age at diagnosis, type of mastectomy and immediate reconstruction, tumor characteristics, and the evaluation of the sentinel axillary lymph node. The mean follow-up period was 30.5 months. RESULTS: In a mean period of 39.13 months, 8 patients (3.67%) developed a recurrence post-mastectomy, 2 of whom with distant metastasis. Two others developed distant metastases subsequently during treatment. All 4 died due to progression of metastases, while the other 4 are alive and disease-free after treatment. The only risk factor was young age at initial diagnosis (<40 years). None of the other factors described in the literature, such as high grade or diffuse disease, comedo-necrosis, positive margins or micro-invasion were statistically significant. CONCLUSION: The recurrence of breast cancer after mastectomy for DCIS is rare, however, it carries a high mortality rate for those who do relapse. Patients who have high risk factors such as young age at diagnosis and high risk tumor factors should be followed closely for signs of recurrence and/or metastasis.

Efficacy and safety of continuous low-irradiance photodynamic therapy in the treatment of chest wall progression of breast cancer.

BACKGROUND: Photodynamic therapy (PDT) is a binary therapy using a drug and high-energy light source. PDT is approved for several premalignant and malignant conditions. Recent in-vitro and animal data suggest that enhanced tumor-specific cytotoxicity can be achieved with far less collateral damage to normal surrounding tissues if PDT is administered continuously at a lower dose rate for extended periods of time. Based on these promising preclinical data, we conducted a Phase I clinical trial of continuous low-irradiance photodynamic therapy (CLIPT) using 630 nm laser energy and intravenously administered porforin sodium as the photosensitizer. We determined the maximum tolerated dose (MTD) of CLIPT on skin and tumor response in subjects with cutaneous and subcutaneous metastatic nodules who had failed radiation and surgery. METHODS: Patients with cutaneous and/or subcutaneous metastatic nodules that had failed radiation and surgery were offered enrollment into the trial. The initial study design planned for sequential cohorts of six subjects to be treated at increasing laser intensity, starting at 100 J/cm(2) administered continuously over 24 h (10(-2) dose rate compared with standard PDT). Dose-limiting toxicity was defined as partial or full-thickness necrosis of the surrounding tumor-free, previously irradiated skin. The MTD was defined as the highest laser energy at which ≤33% of subjects experienced the dose-limiting toxicity. Subjects received intravenous porfirmer sodium 0.8 mg/kg 48 h before commencing CLIPT. Response rates and quality of life measures were assessed. RESULTS: Nine subjects were enrolled with chest wall progression of breast cancer following mastectomy. All had failed prior surgery and electron-beam radiation therapy. The initial two subjects were treated at 100 J/cm(2) and developed partial thickness skin necrosis. Dose reduction was therefore instituted, and the next cohort was treated at 50 J/cm(2). None of the subsequent seven subjects suffered partial or full thickness necrosis, thus establishing the MTD at 50 J/cm(2) over 24 h (0.5 mW irradiance). Six of the nine subjects (67%) had either a complete or partial clinical response. Of note, two subjects had significant regression of tumor nodules distant from the treatment field. Of the eight subjects whose terminal deoxynucleotidyl transferase dUTP nick end labeling assay results were available, 8 (100%) demonstrated histologic response to treatment as evidenced by either tumor apoptosis or regression. Quality of life measures were improved following treatment-particularly bleeding and pain from the tumor nodules. CONCLUSIONS: The MTD of CLIPT was established at 50 J/cm(2) administered continuously over 24 h. These preliminary data suggest CLIPT may be an effective, low-morbidity therapeutic modality in the treatment of cutaneous and subcutaneous metastases of breast cancer following mastectomy. Further evaluation in a larger cohort is warranted to better assess efficacy and optimize the intervention.

Experience of Photodynamic Therapy for Palliation of the Chest Wall and Skin Recurrence in a Patient with Breast Cancer

In patient treated by mastectomy for breast cancer, chest wall and skin recurrences are frequently encountered. Chest wall recurrence results in profound physical and psychological morbidity, and often heralds the appearance of other, more life threatening metastasis. Traditionally the two most common treatments have been site-specific radiation and resection. Photodynamic therapy (PDT) provided an alternative treatment modality using a photosensitizer and laser light to induce selective tumor necrosis. The patient was 64- years old female, had undergone breast conserving surgery for cancer of the right breast. Chest wall and skin metastasis recurred at 40 months after the adjuvant treatment of chemotherapy. The lesions were progressed despite 2nd, 3rd chemotherapy and hyperthermal therapy. The light was administered through a diode laser turned to 630 nm wave length (150 J/cm2 in light dosage, 200 mW/cm2 in intensity), 72 h after photosensitizing agent injection. There was clinical evidence of partial response, defined as granulation tissue with re-epitheliaization from the periphery of normal epithelium. PDT has demonstrated good results in other solid tumors at some hospitals, however there has been no application for breast cancer in Korea previously. Our experience suggests that PDT is non-invasive procedure that is highly tolerable, particularly when compared with other modalities, and an effective treatment method for chest wall or skin recurrence that shows no response to other treatments.