Mina N. Shenouda

The Impact of Radiation Therapy on the Risk of Lymphedema After Treatment for Breast Cancer: A Prospective Cohort Study

PURPOSE/OBJECTIVE Lymphedema after breast cancer treatment can be an irreversible condition with a negative impact on quality of life. The goal of this study was to identify radiation therapy-related risk factors for lymphedema. METHODS AND MATERIALS From 2005 to 2012, we prospectively performed arm volume measurements on 1476 breast cancer patients at our institution using a Perometer. Treating each breast individually, 1099 of 1501 patients (73%) received radiation therapy. Arm measurements were performed preoperatively and postoperatively. Lymphedema was defined as ≥10% arm volume increase occurring >3 months postoperatively. Univariate and multivariate Cox proportional hazard models were used to evaluate risk factors for lymphedema. RESULTS At a median follow-up time of 25.4 months (range, 3.4-82.6 months), the 2-year cumulative incidence of lymphedema was 6.8%. Cumulative incidence by radiation therapy type was as follows: 3.0% no radiation therapy, 3.1% breast or chest wall alone, 21.9% supraclavicular (SC), and 21.1% SC and posterior axillary boost (PAB). On multivariate analysis, the hazard ratio for regional lymph node radiation (RLNR) (SC ± PAB) was 1.7 (P=.025) compared with breast/chest wall radiation alone. There was no difference in lymphedema risk between SC and SC + PAB (P=.96). Other independent risk factors included early postoperative swelling (P<.0001), higher body mass index (P<.0001), greater number of lymph nodes dissected (P=.018), and axillary lymph node dissection (P=.0001). CONCLUSIONS In a large cohort of breast cancer patients prospectively screened for lymphedema, RLNR significantly increased the risk of lymphedema compared with breast/chest wall radiation alone. When considering use of RLNR, clinicians should weigh the potential benefit of RLNR for control of disease against the increased risk of lymphedema.

Is Biological Subtype Prognostic of Locoregional Recurrence Risk in Women With pT1-2N0 Breast Cancer Treated With Mastectomy?

PURPOSE To examine locoregional and distant recurrence (LRR and DR) in women with pT1-2N0 breast cancer according to approximated subtype and clinicopathologic characteristics. METHODS AND MATERIALS Two independent datasets were pooled and analyzed. The study participants were 1994 patients with pT1-2N0M0 breast cancer, treated with mastectomy without radiation therapy. The patients were classified into 1 of 5 subtypes: luminal A (ER+ or PR+/HER 2-/grade 1-2, n=1202); luminal B (ER+ or PR+/HER 2-/grade 3, n=294); luminal HER 2 (ER+ or PR+/HER 2+, n=221); HER 2 (ER-/PR-/HER 2+, n=105) and triple-negative breast cancer (TNBC) (ER-/PR-/HER 2-, n=172). RESULTS The median follow-up time was 4.3 years. The 5-year Kaplan-Meier (KM) LRR were 1.8% in luminal A, 3.1% in luminal B, 1.7% in luminal HER 2, 1.9% in HER 2, and 1.9% in TNBC cohorts (P=.81). The 5-year KM DR was highest among women with TNBC: 1.8% in luminal A, 5.0% in luminal B, 2.4% in luminal HER 2, 1.1% in HER 2, and 9.6% in TNBC cohorts (P<.001). Among 172 women with TNBC, the 5-year KM LRR were 1.3% with clear margins versus 12.5% with close or positive margins (P=.04). On multivariable analysis, factors that conferred higher LRR risk were tumors>2 cm, lobular histology, and close/positive surgical margins. CONCLUSIONS The 5-year risk of LRR in our pT1-2N0 cohort treated with mastectomy was generally low, with no significant differences observed between approximated subtypes. Among the subtypes, TNBC conferred the highest risk of DR and an elevated risk of LRR in the presence of positive or close margins. Our data suggest that although subtype alone cannot be used as the sole criterion to offer postmastectomy radiation therapy, it may reasonably be considered in conjunction with other clinicopathologic factors including tumor size, histology, and margin status. Larger cohorts and longer follow-up times are needed to define which women with node-negative disease have high postmastectomy LRR risks in contemporary practice.

Deep inspiration breath-hold technique in left-sided breast cancer radiation therapy: Evaluating cardiac contact distance as a predictor of cardiac exposure for patient selection

PURPOSE The purpose of this study was to evaluate the efficacy of voluntary deep inspiration breath-hold (DIBH) over a free-breathing (FB) technique to minimize cardiac radiation exposure in radiation therapy of left-sided breast cancer. Also, to better select patients for DIBH, the correlation between cardiac contact distance (CCD) and cardiac dose was assessed. METHODS AND MATERIALS Thirty-five patients with left-sided breast cancer underwent DIBH and FB planning computed tomography scans, and the 2 plans were compared. Dose-volume histograms were analyzed for heart, left anterior descending coronary artery (LAD), left ventricle (LV), and left lung. Axial CCDs and parasagittal CCDs (FB-CCDps) were measured on FB planning computed tomography scans. RESULTS Dose to heart, LAD, LV, and left lung was significantly lower in DIBH plans than in FB by all metrics. When DIBH was compared with FB, mean dose (Dmean) for heart was 0.9 versus 2.5 Gy; for LAD, 4.0 versus 14.9 Gy; and for LV, 1.1 versus 3.9 Gy (P < .0001), respectively. Seventy-five percent of the patients had a dose reduction of ≥ 0.9 Gy in Dmean to heart, ≥ 3 Gy in Dmean to LAD, and ≥ 1.7 Gy in Dmean to LV. FB-CCDps was associated with an equivalent uniform dose to heart, LAD, and LV for both the DIBH and FB plans (P ≤ .01); FB axial CCD measures were not. CONCLUSIONS DIBH is a simple and highly effective technique to reduce cardiac exposure without compromising target coverage. FB-CCDps is potentially a very good predictor for cardiac exposure: the longer the FB-CCDps, the higher the dose. Our findings suggest that at least 75% of patients with left-sided breast cancer might benefit from the DIBH technique in terms of potentially clinically relevant dose reduction to cardiac structures, and therefore, it should be instituted as routine clinical practice.

Outcome Following Local‐Regional Recurrence in Women with Early‐Stage Breast Cancer: Impact of Biologic Subtype

Local‐regional recurrence (LRR) after breast‐conserving therapy (BCT) can result in distant metastasis and decreased disease‐free survival (DFS). This study examines factors associated with DFS following LRR. The initial population included 2,233 consecutive women who underwent BCT from 1998 to 2007. Biologic subtype was approximated using a combination of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. Cumulative incidence of DFS after LRR was calculated. The association of clinical, pathologic, and treatment parameters with DFS was evaluated using a Cox regression model. At a median follow‐up of 105 months, 82 patients (3.7%) had a LRR. Of these, 66 (80%) were in‐breast and 16 (20%) involved the ipsilateral lymph nodes. Twenty patients subsequently developed distant metastases. Five‐year DFS after initial recurrence was 69.6% for the overall cohort. On univariate analysis, triple‐negative disease (ER/PR/HER2 negative, TNBC) was associated with reduced DFS (HR = 3.8; 95% CI: 1.8–8.1; p < 0.001). Other factors associated with reduced DFS were larger tumor size (HR = 1.3; 95% CI: 1.03–1.6; p = 0.02), shorter interval from initial diagnosis to LRR (HR = 0.98 per month; 95% CI: 0.97–0.99; p = 0.02), and no salvage surgery (HR = 0.2; 95% CI: 0.09–0.5; p = 0.001). On multivariate analysis, TNBC remained the most significant factor associated with reduced DFS (HR = 4.8; 95% CI: 2.25–10.4; p < 0.001). Compared to women with luminal A disease, those with TNBC had significantly worse DFS (37.5% versus 88.3% at 5 years; p < 0.001). Women with TNBC who developed LRR were at high risk of subsequent recurrence. Efforts should be targeted toward both preventing initial recurrence and decreasing subsequent metastasis.

Immediate Implant Reconstruction Is Associated With a Reduced Risk of Lymphedema Compared to Mastectomy Alone: A Prospective Cohort Study.

Objective:We sought to determine the risk of lymphedema associated with immediate breast reconstruction compared to mastectomy alone. Background:Immediate breast reconstruction is increasingly performed at the time of mastectomy. Few studies have examined whether breast reconstruction impacts development of lymphedema. Methods:A total of 616 patients with breast cancer who underwent 891 mastectomies between 2005 and 2013 were prospectively screened for lymphedema at our institution, with 22.2 months’ median follow-up. Mastectomies were categorized as immediate implant, immediate autologous, or no reconstruction. Arm measurements were performed preoperatively and during postoperative follow-up using a Perometer. Lymphedema was defined as 10% or more arm volume increase compared to preoperative. Kaplan-Meier and Cox regression analyses were performed to determine lymphedema rates and risk factors. Results:Of 891 mastectomies, 65% (580/891) had immediate implant, 11% (101/891) immediate autologous, and 24% (210/891) no reconstruction. The two-year cumulative incidence of lymphedema was as follows: 4.08% [95% confidence interval (CI): 2.59–6.41%] implant, 9.89% (95% CI: 4.98–19.1%) autologous, and 26.7% (95% CI: 20.4–34.4%) no reconstruction. By multivariate analysis, immediate implant [hazards ratio (HR): 0.352, P < 0.0001] but not autologous (HR: 0.706, P = 0.2151) reconstruction was associated with a significantly reduced risk of lymphedema compared to no reconstruction. Axillary lymph node dissection (P < 0.0001), higher body mass index (P < 0.0001), and greater number of nodes dissected (P = 0.0324) were associated with increased lymphedema risk. Conclusions:This prospective study suggests that in patients for whom implant-based reconstruction is available, immediate implant reconstruction does not increase the risk of lymphedema compared to mastectomy alone.

Do locoregional recurrence and survival outcomes differ in women with node-negative, HER2-positive breast cancer treated with breast-conserving therapy versus mastectomy?

69 Background: Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer subtype is an adverse prognostic factor, it is unclear whether there are differences in outcomes according to the type of locoregional treatment used in this population. This study compared locoregional recurrence and survival outcomes in women with node-negative, HER2-positive breast cancer treated with Breast Conserving Therapy (BCT) versus Modified Radical Mastectomy (MRM). METHODS Independent datasets from the BC Cancer Agency (BCCA) and the Massachusetts General Hospital (MGH) were pooled and analyzed. Study subjects included 748 patients between 2003-2009 with pT1-2, N0, M0 Her2+ breast cancer, treated with BCT or MRM. Standard clinico-pathologic factors were analyzed. Kaplan-Meier locoregional recurrence (LRR), breast cancer specific survival (BCSS) and overall survival (OS) were compared between cohorts treated with BCT vs. MRM. Multivariable analysis (MVA) with Cox regression modeling was performed to evaluate the prognostic significance of type of locoregional treatment on outcomes. RESULTS Median follow-up time was 4.2 years for BCCA and 6.0 years for MGH. Comparison of clinico-pathologic factors according to type of locoregional treatment found that patients treated with MRM had higher proportions of grade 3 histology (69% vs. 60%, p = 0.004) and PR-negative disease (56% vs. 44%, p = 0.008) and lower rates of endocrine therapy (51% vs. 64%, p <0.001) and herceptin therapy (50% vs. 57%, p = 0.04). There were no significant differences between BCT and MRM groups in 5-year Kaplan-Meier LRR (2.0% vs. 1.7%, p=0.88), BCSS (97.2% vs. 96.1%, p=0.70), and OS (95.5% vs. 93.4%, p=0.19). On MVA, BCT and MRM were associated with similar LRR, BCSS, and OS. The only factor associated with reduced OS was T2 disease (HR 3.1, p=0.01). CONCLUSIONS In this multi-institutional study, no significant outcome differences were found among women with T1-2 N0, HER2-positive breast cancer treated with BCT or MRM. Breast conserving therapy is safe in this population, providing high rates of locoregional control and survival equivalent to mastectomy.

Abstract P6-09-04: The Association of Low Level Arm Volume Increases with Lymphedema Symptoms Following Treatment for Breast Cancer

Purpose/Objective: The symptoms associated with breast cancer-related lymphedema are well-documented, and include sensations of heaviness, swelling, and tightness in the upper extremity and trunk. However, the clinical significance of low-level arm volume changes frequently experienced by breast cancer patients is not well understood. We sought to determine the association of low level arm volume changes with patient-reported lymphedema symptoms in women treated for breast cancer. Methods: 267 patients who underwent surgical treatment for breast cancer from 2010–2012 were identified from a cohort of patients prospectively screened for lymphedema at our institution. Patients were assessed with perometer arm volume measurements and a survey of lymphedema symptoms pre and post operatively, and at 3–7 month intervals thereafter. Inclusion in this analysis was limited to unilaterally affected women with ≥ 3 assessments and ≥ 6 months of post-surgical follow-up. Arm volume changes were quantified as Relative Volume Change (RVC): RVC = (A2*U1)/(U2*A1) − 1, where A1 is pre-operative arm volume and A2 is post-operative arm volume on the affected side, and U1 and U2 are arm volumes on the unaffected side at these time points. Low level arm volume change was defined as a measurement with RVC ≥ 5% Results: Low level arm volume changes occurred in 21.7% (58/267) of patients during the follow-up period at a median of 10.4 months post-operatively. Median post-operative follow-up was 12.4 months and 5 assessments per patient. By actuarial univariate analysis, symptoms of larger arm, shoulder, or neck (p Conclusions: This data suggests that patients may be symptomatic for lymphedema even when experiencing low level arm volume changes. These patients should be followed closely for progression of measured arm volume or heightened lymphedema symptoms suggesting progression of the condition. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-09-04.