Locoregional Breast Cancer Research Articles

Assessment of predictors and prognostic factors for locoregional recurrent breast cancer

Background: Assessment of predictors and prognostic factors of locoregional recurrent breast cancer will help in management of those patients. The aim of this study was to assess and identify the predictors and prognostic factors for locoregional current breast cancer.Methods: This prospective study will be carried out on 50 female patients with history of breast cancer underwent surgical procedures either modified radical mastectomy (MRM) or conservative breast surgery (CBS) and adjuvant therapy (chemotherapy, radiotherapy, hormonal therapy).Results: Significant relationship between recurrence of breast cancer and Oral contraceptive pills of the studied female patients with history of breast cancer underwent surgery.Conclusions: Number of positive lymph nodes, lympho-vascular invasion, positive safety margin and presence of extensive intra-ductal component all these factors increase risk of recurrent breast cancer.

ASO Author Reflections: Use of Breast Imaging After Treatment for Locoregional Breast Cancer (AFT-01).

ASO Author Reflections: Use of Breast Imaging After Treatment for Locoregional Breast Cancer (AFT-01).

Chemotherapy-induced fatigue is associated with changes in gene expression in the peripheral blood mononuclear cell fraction of patients with locoregional breast cancer.

Chemotherapy-induced fatigue (CIF) is a frequent symptom that impairs patient functioning and quality of life. We aimed to evaluate whether systemic chemotherapy can induce a specific gene expression profile in peripheral blood mononuclear cells (PBMNC) of patients with locoregional breast cancer (LRBC) who develop CIF. PBMNC were collected from 3 patients who developed CIF before and after their initial cycle of chemotherapy, and RNA-seq was performed in an Ion Torrent™ System. A total of 12.345 transcripts were sequenced, of which 26 were selected out of 71 that had significantly different expression before and after chemotherapy. The RNA-seq results were validated by RT-qPCR in a different group of 28 patients with LRBC who developed CIF after their first cycle of chemotherapy and in six patients who also received chemotherapy but did not develop CIF (controls). We assessed CIF according the BFI and Chalder Questionnaires. We observed a significant increase in expression of DUSP18 and RHOBTB1 and decreased expression of NCAN and RAET1G in patients who developed CIF after chemotherapy. Control patients only exhibited a significant decrease in NCAN expression. CIF induces specific changes in gene expression in the PBMNC of LRBC patients. Some of these changes, such as downregulation of NCAN expression, may reflect direct effects of chemotherapy since they are also observed in the controls. Furthermore, CIF may involve downregulation of skeletal muscle genes (RHOBT1, DUSP18) and immune systems (RAETG1), whereas NCAN downregulation may underlie the adverse cognitive effects of chemotherapy.

Management of Loco-Regional Recurrent Breast Cancer after Prior Radiation to the Breast or Chest Wall

Management of Loco-Regional Recurrent Breast Cancer after Prior Radiation to the Breast or Chest Wall

Early-Onset Breast Cancer: Effect of Diagnosis and Therapy on Fertility Concerns, Endocrine System, and Sexuality of Young Mothers in Germany

Background: The purpose of this study was to analyze the effect of breast cancer therapy on fertility concerns and sexuality of young mothers with breast cancer in Germany. Methods: During a mother-child rehabilitation program, 1,191 young mothers with locoregional primary breast cancer, treated between 2006 and 2014, were recruited. Data included sociodemographic data, TNM stage, tumor biology, therapies, and patient-reported outcomes such as sexuality and fertility concerns. Results: The mean age at diagnosis was 40 years. Approximately a quarter of the patients stated that family planning had not been completed at the time of diagnosis. Nearly half of all patients had been informed as to how treatment could affect fertility, but counseling at a specialized fertility center was offered to only 13%. Of all patients, 4% took a consultation and 2% underwent fertility preservation procedures. Conclusion: Our study indicates that only a minority of patients is referred to fertility centers although family planning is incomplete at the time of diagnosis in about 25% of young women with breast cancer. Thus, these patients should not only be informed about the effects of treatment on fertility and sexuality, but should be referred to a fertility center.

Obesity and mortality after locoregional breast cancer diagnosis.

Higher mortality after a breast cancer diagnosis has been observed among women who are obese. We investigated the relationships between body mass index (BMI) and all-cause or breast cancer-specific mortality after a diagnosis of locoregional breast cancer. Women diagnosed in 2004 with AJCC Stage I, II, or III breast cancer (n = 5394) were identified from a population-based National Program of Cancer Registries (NPCR) patterns of care study (POC-BP) drawing from registries in seven U.S. states. Differences in overall and breast cancer-specific mortality were investigated using Cox proportional hazards regression models adjusting for demographic and clinical covariates, including age- and stage-based subgroup analyses. In women 70 or older, higher BMI was associated with lower overall mortality (HR for a 5kg/m2 difference in BMI = 0.85, 95% CI 0.75-0.95). There was no significant association between BMI and overall mortality for women under 70. BMI was not associated with breast cancer death in the full sample, but among women with Stage I disease; those in the highest BMI category had significantly higher breast cancer mortality (HR for BMI ≥ 35kg/m2 vs. 18.5-24.9kg/m2 = 4.74, 95% CI 1.78-12.59). Contrary to our hypothesis, greater BMI was not associated with higher overall mortality. Among older women, BMI was inversely related to overall mortality, with a null association among younger women. Higher BMI was associated with breast cancer mortality among women with Stage I disease, but not among women with more advanced disease.

Dose variability in different lymph node levels during locoregional breast cancer irradiation: the impact of deep-inspiration breath hold.

Aim of the present analysis was to evaluate the movement and dose variability of the different lymph node levels of node-positive breast cancer patients during adjuvant radiotherapy(RT) with regional nodal irradiation (RNI) in deep-inspiration breath hold (DIBH). Thirty-five consecutive node-positive breast cancer patients treated from October 2016 to February 2018 receiving postoperative RT of the breast or chest wall including RNI of the supra-/infraclavicular lymph node levels (corresponding to levelsIV, III, Rotter LN (interpectoral), and some parts of levelII) were analyzed. To evaluate the lymph node level movement, acenter of volume (COV) was obtained for each lymph node level for free-breathing (FB) and DIBH plans. Geometric shifts and dose differences between FB and DIBH were analyzed. Asignificant movement of the COV in anterior(y) and cranial(z) dimensions was observed for lymph node levelsI-II and Rotter lymph nodes (p < 0.001) due to DIBH. Only minor changes in the lateral dimension (xaxis) were observed, without reaching significance for levelsIII, IV, and internal mammary. There was asignificant difference in the mean dose of levelI (DIBH vs. FB: 38.2 Gy/41.3 Gy, p < 0.001) and levelII (DIBH vs. FB: 45.9 Gy/47.2 Gy, p < 0.001), while there was no significant difference in levelIII (p = 0.298), levelIV (p = 0.476), or internal mammary nodes (p = 0.471). Asignificant movement of the axillary lymph node levels was observed during DIBH in anterior and cranial directions for node-positive breast cancer patients in comparison to FB. The movement leads to asignificant dose reduction in levelI and levelII.

Evaluation of a Novel Field-placement Algorithm for Locoregional Breast Cancer Radiotherapy Including the Internal Mammary Chain

AimsIrradiation of the internal mammary chain (IMC) is increasing following recently published data, but the need for formal delineation of lymph node volumes is slowing implementation in some healthcare settings. A field-placement algorithm for irradiating locoregional lymph nodes including the IMC could reduce the resource impact of introducing irradiation of the IMC. This study describes the development and evaluation of such an algorithm. Materials and methodsAn algorithm was developed in which six points representing lymph node clinical target volume borders (based on European Society for Radiotherapy and Oncology consensus nodal contouring guidelines) were placed on computed tomography-defined anatomical landmarks and used to place tangential and nodal fields. Single-centre testing in 20 cases assessed the success of the algorithm in covering planning target volumes (PTVs) and adequately sparing organs at risk. Plans derived using the points algorithm were also compared with plans generated following formal delineation of nodal PTVs, using the Wilcoxon signed rank test. Timing data for point placement were collected. Multicentre testing using the same methods was then carried out to establish whether the technique was transferable to other centres. ResultsSingle-centre testing showed that 95% of cases met the nodal PTV coverage dose constraints (binomial probability confidence interval 75.1–99.9%) with no statistically significant reduction in mean heart dose or ipsilateral lung V17Gy associated with formal nodal delineation. In multicentre testing, 69% of cases met nodal PTV dose constraints and there was a statistically significant difference in IMC PTV coverage using the points algorithm when compared with formally delineated nodal volumes (P < 0.01). However, there was no difference in axillary level 1–4 PTV coverage (P = 0.11) with all cases meeting target volume constraints. ConclusionsThe optimal strategy for breast and locoregional lymph node radiotherapy is target volume delineation. However, use of this novel points-based field-placement algorithm results in dosimetrically acceptable plans without the need for formal lymph node contouring in a single-centre setting and for the breast and level 1–4 axilla in a multicentre setting. Further quality assurance measures are needed to enable implementation of the algorithm for irradiation of the IMC in a multicentre setting.

Locoregional Breast Cancer Surgery: Is there a Role in the Presence of Metastatic Disease?

Locoregional Breast Cancer Surgery: Is there a Role in the Presence of Metastatic Disease?

Effectiveness of biomarker surveillance after treatment in locoregional breast cancer.

e12608Background: Utilization of the biomarkers CA 15-3 and CA 27.29 to monitor recurrence or metastases does not improve outcomes after treatment in locoregional breast cancer. We sought to determ...

A National Study of the Use of Asymptomatic Systemic Imaging for Surveillance Following Breast Cancer Treatment (AFT-01).

Although not guideline recommended, studies suggest 50% of locoregional breast cancer patients undergo systemic imaging during follow-up, prompting its inclusion as a Choosing Wisely measure of potential overuse. Most studies rely on administrative data that cannot delineate scan intent (prompted by signs/symptoms vs. asymptomatic surveillance). This is a critical gap as intent is the only way to distinguish overuse from appropriate care. Our aim was to assess surveillance systemic imaging post-breast cancer treatment in a national sample accounting for scan intent. A stage-stratified random sample of 10 women with stage II-III breast cancer in 2006-2007 was selected from each of 1217 Commission on Cancer-accredited facilities, for a total of 10,838 patients. Registrars abstracted scan type (computed tomography [CT], non-breast magnetic resonance imaging, bone scan, positron emission tomography/CT) and intent (cancer-related vs. not, asymptomatic surveillance vs. not) from medical records for 5years post-diagnosis. Data were merged with each patient's corresponding National Cancer Database record, containing sociodemographic and tumor/treatment information. Of 10,838 women, 30% had one or more, and 12% had two or more, systemic surveillance scans during a 4-year follow-up period. Patients were more likely to receive surveillance imaging in the first follow-up year (lower proportions during subsequent years) and if they had estrogen receptor/progesterone receptor-negative tumors. Locoregional breast cancer patients undergo asymptomatic systemic imaging during follow-up despite guidelines recommending against it, but at lower rates than previously reported. Providers appear to use factors that confer increased recurrence risk to tailor decisions about systemic surveillance imaging, perhaps reflecting limitations of data on which current guidelines are based. ClinicalTrials.gov Identifier: NCT02171078.

Simulation Modeling of Cancer Clinical Trials: Application to Omitting Radiotherapy in Low-risk Breast Cancer.

We used two models to simulate a proposed noninferiority trial of radiotherapy (RT) omission in low-risk invasive breast cancer to illustrate how modeling could be used to predict the trial's outcomes, inform trial design, and contribute to practice debates. The proposed trial was a prospective randomized trial of no-RT vs RT in women age 40 to 74 years undergoing lumpectomy and endocrine therapy for hormone receptor-positive, human epidermal growth factor receptor 2-negative, stage I breast cancer with an Oncotype DX score of 18 or lower. The primary endpoint was recurrence-free interval (RFI), including locoregional recurrence, distant recurrence, and breast cancer death. Noninferiority required the two-sided 90% confidence interval of the RFI hazard ratio (HR) for no-RT vs RT to be entirely below 1.7. Model inputs included published data. The trial was simulated 1000 times, and results were summarized as percent concluding noninferiority and mean (standard deviation) of hazard ratios for Model GE and Model M, respectively. Noninferiority was demonstrated in 18.0% and 3.7% for the two models. The respective means (SD) of the RFI hazard ratios were 1.8 (0.7) and 2.4 (0.9); most were locoregional recurrences. The mean five-year RFI rates for no-RT vs RT (SD) were 92.7% (2.9%) vs 95.5% (2.2%) and 88.4% (2.0%) vs 94.5% (1.6%). Both models showed little or no difference in breast cancer-specific or overall survival. Alternative definitions of low risk based on combinations of age and grade produced similar results. The proposed trial was unlikely to show noninferiority of omitting radiotherapy even using alternative definitions of low-risk, as the endpoint included local recurrence. Future trials regarding radiotherapy should address absolute reduction in recurrence and impact of type of recurrence on the patient.

OC-0308: Error in node level positioning after 3D CBCT match in loco-regional breast cancer radiotherapy

OC-0308: Error in node level positioning after 3D CBCT match in loco-regional breast cancer radiotherapy

EP-2047: Surface guided radiotherapy increases setup accuracy for locoregional breast cancer patients

EP-2047: Surface guided radiotherapy increases setup accuracy for locoregional breast cancer patients

330 (PB-125) - Management of local and locoregional triple-negative breast cancer

330 (PB-125) - Management of local and locoregional triple-negative breast cancer

2 - Very low risk of locoregional breast cancer recurrence in the EORTC 10041/BIG 03-04 MINDACT trial: Analysis of risk factors including the 70-gene signature

2 - Very low risk of locoregional breast cancer recurrence in the EORTC 10041/BIG 03-04 MINDACT trial: Analysis of risk factors including the 70-gene signature

Use of Breast Imaging After Treatment for Locoregional Breast Cancer(AFT-01).

Annual mammography is recommended after breast cancer treatment. However, studies suggest its under-utilization for Medicare patients. Utilization in the broader population is unknown, as is the role of breast magnetic resonance imaging (MRI). Understanding factors associated with imaging use is critical to improvement of adherence to recommendations. A random sample of 9835 eligible patients receiving surgery for stages 2 and 3 breast cancer from 2006 to 2007 was selected from the National Cancer Database for primary data collection. Imaging and recurrence data were abstracted from patients 90days after surgery to 5years after diagnosis. Factors associated with lack of imaging were assessed using multivariable repeated measures logistic regression with generalized estimating equations. Patients were censored for death, bilateral mastectomy, new cancer, and recurrence. Of 9835 patients, 9622, 8702, 8021, and 7457 patients were eligible for imaging at surveillance years 1 through 4 respectively. Annual receipt of breast imaging declined from year 1 (69.5%) to year 4 (61.0%), and breast MRI rates decreased from 12.5 to 5.8%. Lack of imaging was associated with age 80years or older and age younger than 50years, black race, public or no insurance versus private insurance, greater comorbidity, larger node-positive hormone receptor-negative tumor, excision alone or mastectomy, and no chemotherapy (p < 0.005). Receipt of breast MRI was associated with age younger than 50years, white race, higher education, private insurance, mastectomy, chemotherapy, care at a teaching/research facility, and MRI 12months before diagnosis (p < 0.05). Under-utilization of mammography after breast cancer treatment is associated with sociodemographic and clinical factors, not institutional characteristics. Effective interventions are needed to increase surveillance mammography for at-risk populations. ClinicalTrials.gov Identifier: NCT02171078.

Abstract P5-01-02: Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results

Abstract Purpose: To report preliminary data in a pilot study evaluating the ability of Tc99m sestamibi Molecular Breast Imaging (MBI) to predict response and assess residual disease at the completion of neoadjuvant chemotherapy (NAC) in breast cancer patients. Materials and Methods: Patients with localized, invasive breast cancer (T1-T4, N0-N3, M0) planned for NAC were enrolled in this prospective IRB approved clinical trial. All patients had digital mammography (DM), ultrasound (US), and MBI at baseline (T0), after 2 NAC cycles (T1), and at after NAC completion (T2). Tumor size and volume changes were compared with residual disease at surgery. MBI images were corrected for scatter and attenuation using a novel approach and regions of interest (ROI) were drawn over tumors to compute three quantitative MBI uptake metrics for correlation with pathologic response: tumor to background ratio (TBR), fractional activity uptake (FAU), and MBI-specific standardized uptake value (SUV). ROC analysis was performed. Results: Patients (n=25) who completed NAC, had 75 imaging time points and had surgery, were included in this analysis. Median age was 49 years (range 31 -77). Eleven patients (11/25, 44%) had complete pathologic response (pCR). Absolute TBR values after 2 cycles (T1) and before surgery (T2) had highest correlation with pCR (AUC 0.81; 95% CI 0.63 to 0.99, p=0.01, and AUC 0.78; 95% CI 0.59 to 0.97, p=0.015, respectively). Change in SUV after 2 cycles, Δ SUV1 (T1-T0), (AUC 0.84; 95% CI 0.66 to 1.00, p=0.01) and change in SUV prior to surgery, Δ SUV2 (T2-T0) (AUC 0.80; 95% CI 0.60 to 1.00, p=0.02), were most predictive of pCR. Tumor size and volume showed modest specificity for detecting residual disease, and was highest for MBI (79%), followed by MMG (64%), and lowest for US (55%). Conclusion: Quantitative MBI metrics show promise for the prediction of pCR in breast cancer patients undergoing NAC. Establishment of quantitative metrics for the early prediction of tumor response during NAC of breast cancer patients may provide an alternate to influencing NAC choice early in the management algorithm. Further investigation with a larger sample size is warranted. Citation Format: Rauch GM, Adrada BE, Kappadath C, Candelaria RP, Huang ML, Santiago L, Moseley T, Scoggins ME, Knudtson JD, Lopez BP, Hess KR, Krishnamurthy S, Moulder S, Valero V, Yang W. Quantitative assessment of tumor response to neoadjuvant chemotherapy in women with locoregional invasive breast cancer using Tc99m sestamibi molecular breast imaging - preliminary results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-01-02.

Abstract P1-15-05: Oncologists' perception of anti-estrogen therapy benefit

Abstract Background Recent publication of Suppression of Ovarian Function (SOFT) and Tamoxifen and Exemestane (TEXT) trials provides additional options for premenopausal women with hormone receptor (HR)-positive breast cancer in improving estrogen blockade - tamoxifen (T) plus ovarian function suppression (OFS) and aromatase inhibitors (AI) plus OFS. Analysis of these trials conclude that, for a premenopausal woman with HR-positive breast cancer with high risk features for recurrence have an absolute benefit for five-year breast cancer free interval (BCFI) would be 5% with the use of T + OFS and 10 - 15% with AI + OFS compared to the usof T-alone. However, therapeutic option decision-making is dependent on the oncologists' perception of the benefit and risk for adjuvant anti-estrogen therapy. We aimed to evaluate an oncologist's perception of the absolute benefit for anti-estrogen therapy options in HR–positive breast cancer and identify predictors for variations in perceptions of benefit. Methods We designed a survey using a clinical vignette of a young, premenopausal woman with stage IIIA HR-positive breast cancer with high risk of recurrence. After obtaining Institutional Review Board (IRB) approval from the University of Kentucky, we sent online and paper survey forms to a convenience sample of 510 oncologists in the United States. Using a scale between 0 and 100, the oncologists were asked to estimate the five-year BCFI (first occurrence of invasive locoregional, distant or contralateral breast cancer) for a woman with similar characteristics if treated with the following: 1) lumpectomy (L) + Radiation (RT); 2) L + RT + chemotherapy (C); 3) L + RT + C + T x five years; 4) L + RT + C + T + OFS; and 5) L + RT + C + AI + OFS. Baseline demographics such as gender, practice setting (academic vs community), years in practice and proportion of breast cancer patients in practice were also collected. Results The highest estimated mean five-year BCFI for the study patient was 76.5% with the addition of AI + OFS to L + RT + C. The estimated absolute benefit for anti-estrogen therapy options: T + OFS vs T-alone was 3.4% (95% CI: 2.7 – 4.0) and for AI + OFS vs T-alone was 5.9% (95% CI: 5.1 – 6.7). Oncologists' Perception of Absolute Benefit Therapy in Premenopausal Women with Breast CancerAnti-Estrogen Therapy5-year BCFI (mean)Standard DeviationL+ RT43.6+/- 18.6L + RT + C59.5+/- 15.5L + RT + C + T x 5 year70.6+/- 13.4L + RT + C + T + OFS74.1+/- 12.9L + RT + C + AI + OFS76.5+/- 12.7 There was no difference in perception of benefit with these anti-estrogen therapy options by gender, practice setting, years in practice or proportion of breast cancer patients seen in practice. Discussion Regardless of their gender, practice setting, clinical experience or volume of breast cancer patients, oncologists significantly underestimate the absolute benefit for various estrogen blockade therapies when compared to the estimated benefit of data from randomized, controlled SOFT and TEXT clinical trial data. We highlight an area for improvement in quality of care that offers an immediate impact on positive outcomes for large numbers of premenopausal women with breast cancer. Citation Format: Patel RA, Maxwell S, Yan D, Dressler E, Mathew A. Oncologists' perception of anti-estrogen therapy benefit [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-05.

Abstract P2-11-19: Safety and efficacy of re-irradiation for locoregional breast cancer recurrences using pulsed reduced dose rate technique and concurrent capecitabine

Abstract Purpose: Locoregionally recurrent breast cancer presents a tremendous therapeutic challenge, but successful treatment can provide a durable cure. Re-irradiation has been performed infrequently in the recurrent setting due to concern for toxicity. Pulsed reduced dose rate radiation is a technique that can decrease the toxicity of re-irradiation by increasing normal tissue repair. Here, we update our previously published results of chest wall re-irradiation with an additional 16 patients and a focus on outcomes and long term toxicities. Methods: Patients treated from 11/09/2000 to 04/21/2016 with pulsed reduced dose rate radiation therapy at the University of Wisconsin were identified by query of Aria radiation oncology record software. Patients were retreated to a median dose of 54 Gy (range 37.5-66 Gy) using pulsed reduced does rate technique, delivering radiation at an apparent dose rate of 0.067 Gy/min to allow for normal tissue repair. The median cumulative dose was 109.8 Gy (range 75 to 236 Gy). Eleven patients underwent comprehensive re-irradiation to the chest wall and locoregional lymphatics, while the remainder underwent re-treatment limited to the site of recurrence. Concurrent capecitabine was given to 15 patients, most frequently at 500mg BID (range 1000 mg to 1500mg daily). The Kaplan-Meier method was used for survival analysis. Results: Thirty-three patients were identified who were treated with pulsed reduced dose rate radiation therapy for locoregionally recurrent invasive breast cancer with a median follow-up of 19.8 months (range 6.8-133.8 months). Sixteen patients were treated with curative intent and 17 patients were treated with palliative intent. Twenty-two patients had gross disease present at the time of treatment, 6 patients had microscopically positive surgical margins, and 5 patients were treated who had negative margins. The 2 year locoregional recurrence free survival was 70.5% by the Kaplan-Meier method for all patients and 81.5% for patients treated with curative intent. Two year overall survival was 43.6% for all patients and 72.2% in patients treated with curative intent. The rate of acute grade 3 skin toxicity was 21.2%. No other acute grade three toxicities occurred. A total of 9 patients (27.2%) developed late grade 3 or greater toxicities, including 4 patients who developed lymphedema, 4 patients who developed non-healing wounds, and one patient who developed both lymphedema and a non-healing wound. Conclusion: Pulsed reduced dose rate radiation therapy with capecitabine is an effective method for treating patients with recurrent breast cancer. The moderate risk of toxicity is warranted in a subset of patients with high risk of disease recurrence or morbidity from disease progression. Further work, including prospective studies, is needed to determine the patients who who will benefit most from this technique. Citation Format: Burr A, Howard S. Safety and efficacy of re-irradiation for locoregional breast cancer recurrences using pulsed reduced dose rate technique and concurrent capecitabine [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-11-19.