The Lack of Consensus of International Contouring Guidelines for the Dorsal Border of the Chest Wall Clinical Target Volume: What is the Impact on Organs at Risk and Relationships to Patterns of Recurrence in the Modern Era?

PURPOSE: Variation exists in cooperative group recommendations for the dorsal border for the chest wall clinical target volume (CTV). We aimed to quantify the impact of this variation on doses to critical organs and examine patterns of chest wall recurrence relative to the pectoralis muscle. METHODS AND MATERIALS: We retrospectively assessed patterns of chest wall recurrence quantified to the recommended CTV borders for women treated between 2005 and 2017. We compared treatment plans for 5 women who were treated with left postmastectomy radiation therapy, with the chest wall contoured using varying dorsal borders for CTV: (1) Anterior pleural surface (Radiation Therapy Oncology Group), (2) anterior surface of pectoralis major (European Society for Radiotherapy and Oncology), and (3) anterior rib surface (institutional practice). Treatment plans were generated for 50 Gy in 25 fractions. Doses to organs-at-risk were compared using paired-sample t tests. RESULTS: Institutional patterns of chest wall recurrence were 64.7% skin and subcutaneous tissue, 23.5% both anterior to and between the pectoralis muscles, and 11.8% isolated to the tissue between the pectoralis major and minor. No chest wall recurrences were noted deep to pectoralis minor. When comparing the plans generated per the Radiation Therapy Oncology Group versus European Society for Radiotherapy and Oncology contouring guidelines, the mean lung V20Gy, heart mean dose, and left anterior descending artery mean dose were 33.5% versus 29.4% (P < .01), 5.2 Gy versus 3.2Gy (P = .02), and 27.3Gy versus 17.8Gy (P = .04), respectively. CONCLUSIONS: The recommended variations in the dorsal chest wall CTV border have significant impact on doses to the heart and lungs. Although our study was limited by small numbers, our institutional patterns of recurrence would support a more anterior dorsal border for the chest wall CTV consistent with older literature.

Combination of Eribulin and Aurora A Inhibitor MLN8237 Prevents Metastatic Colonization and Induces Cytotoxic Autophagy in Breast Cancer.

Recent findings suggest that the inhibition of Aurora A (AURKA) kinase may offer a novel treatment strategy against metastatic cancers. In the current study, we determined the effects of AURKA inhibition by the small molecule inhibitor MLN8237 both as a monotherapy and in combination with the microtubule-targeting drug eribulin on different stages of metastasis in triple-negative breast cancer (TNBC) and defined the potential mechanism of its action. MLN8237 as a single agent and in combination with eribulin affected multiple steps in the metastatic process, including migration, attachment, and proliferation in distant organs, resulting in suppression of metastatic colonization and recurrence of cancer. Eribulin application induces accumulation of active AURKA in TNBC cells, providing foundation for the combination therapy. Mechanistically, AURKA inhibition induces cytotoxic autophagy via activation of the LC3B/p62 axis and inhibition of pAKT, leading to eradication of metastases, but has no effect on growth of mammary tumor. Combination of MLN8237 with eribulin leads to a synergistic increase in apoptosis in mammary tumors, as well as cytotoxic autophagy in metastases. These preclinical data provide a new understanding of the mechanisms by which MLN8237 mediates its antimetastatic effects and advocates for its combination with eribulin in future clinical trials for metastatic breast cancer and early-stage solid tumors. Mol Cancer Ther; 15(8); 1809-22. ©2016 AACR.

Role of obesity and exercise in breast cancer survivors.

Over 60% of the American population meets the criteria for obesity, and obesity is very common in patients with breast cancer. Many studies have shown that obese patients with breast cancer have a worse prognosis compared to normal weight individuals. Tumor characteristics and other factors contribute to this. Exercise could reverse some of the pathophysiologic factors that contribute to this increased risk, and has been shown in some studies to improve survival in patients with breast cancer. In addition to administering anticancer therapy, cancer clinicians should make concerted attempts to get patients to enroll in weight management and exercise programs, which could improve survival in patients with breast cancer.

Surgical resection of the primary tumor, chest wall control, and survival in women with metastatic breast cancer.

BACKGROUND: Among women presenting with de novo stage IV breast cancer, 35% to 60% undergo local therapy, presumably to avoid uncontrolled chest wall disease. Several studies suggest that resection of the primary tumor may prolong survival, but chest wall outcome data are notably lacking. The authors reviewed chest wall status, time to first progression (TTFP), and overall survival (OS) in this group of women. METHODS: Women presenting at the Lynn Sage Breast Center (1995-2005) with an intact primary tumor and stage IV breast cancer or postoperative diagnosis of distant metastases were identified. Logistic regression and Cox proportional hazards models, adjusted for relevant covariates, were used to examine associations between surgical treatment and chest wall status, TTFP, and OS. RESULTS: Of 111 eligible women, 47 (42%) underwent early resection of the primary tumor. Chest wall status was available for 103 women. Local control was maintained in 36 of 44 (82%) patients in the surgical group versus 20 of 59 (34%) patients without surgery (P = .001). TTFP was prolonged in the surgical group (adjusted hazards ratio [HR], 0.493; P = .015). The adjusted HR for OS in the surgical group was 0.798 (P = .520). Chest wall control was associated with improved OS regardless of whether surgical resection of the tumor was performed (HR, 0.415; P < .0002). CONCLUSIONS: These data support the notion that improved local control may play a role in improving outcomes in women with stage IV breast cancer, and resection of in-breast tumors can help to achieve this. A randomized trial is needed to rule out selection bias as an explanation for these findings.

Image-guided procedures for breast masses.

Breast cancer is a disease affecting millions of women worldwide. In the United States, the institution of screening mammography protocols has increased the number of suspicious breast abnormalities requiring diagnostic intervention. Up to 80% of these lesions are benign, forcing the medical community to devise minimally invasive techniques for tissue sampling. A reduction in the number of needle-localized open breast biopsies reduces the morbidity and cost associated with image-detected breast masses. Ultrasound, stereotaxis, and MRI are excellent modalities for detection of breast cancers. Image-guided, large-core biopsy systems have been developed for each of these imaging modalities, enabling successful and accurate tissue sampling and, ultimately, diagnosis of a suspicious lesion. Care must be taken to ensure correlation between imaging findings and pathologic diagnosis; if the two are discordant, further investigation is mandatory. There remains a role for needle-localized open breast biopsy, although is has been reduced significantly. Some patients prefer this method of diagnosis, and in others further investigation in required because of discordant findings. When the documented pathology of the breast abnormality is ADH, ALH, or LCIS, the patient should undergo surgical excision because of the possibility of DCIS or invasive disease in the same area. Some lesions are inaccessible with the current imaging modalities and biopsy systems available. Minimally invasive, image-guided biopsy for breast masses promises to continue to evolve, enabling physicians to diagnose breast cancer with a high degree of accuracy without significant morbidity.