Purpose
Public safety net hospitals (SNH) serve a disparate patient population; however, little is known about long-term oncologic outcomes of patients receiving care at these facilities. This study ...is the first to examine overall survival (OS) and the initiation of treatment in breast cancer patients treated at a SNH.
Methods
Patients presenting to a SNH with stage I-IV breast cancer from 2005 to 2017 were identified from the local tumor registry. The hospital has a weekly breast tumor board and a multidisciplinary approach to breast cancer care. Kaplan-Meier survival analysis was performed to identify patient, tumor, and treatment characteristics associated with OS. Factors with a
p
< 0.1 were included in the Cox proportional hazards model.
Results
2709 breast cancer patients were evaluated from 2005 to 2017. The patient demographics, tumor characteristics, and treatments received were analyzed. Five-year OS was 78.4% (93.9%, 87.4%, 70.9%, and 23.5% for stages I, II, III, and IV, respectively). On multivariable analysis, higher stage, age > 70 years, higher grade, and non-Hispanic ethnicity were associated with worse OS. Patients receiving surgery (HR = 0.33,
p
< 0.0001), chemotherapy (HR = 0.71,
p
= 0.006), and endocrine therapy (HR = 0.61, p < 0.0001) had better OS compared to those who did not receive these treatments.
Conclusion
Despite serving a vulnerable minority population that is largely poor, uninsured, and presenting with more advanced disease, OS at our SNH approaches national averages. This novel finding indicates that in the setting of multidisciplinary cancer care and with appropriate initiation of treatment, SNHs can overcome socioeconomic barriers to achieve equitable outcomes in breast cancer care.
Indications for sentinel lymph node biopsy (SLNB) for thin melanoma are continually evolving. We present a large multi-institutional study to determine factors predictive of sentinel lymph node (SLN) ...metastasis in thin melanoma.
Retrospective review of the Sentinel Lymph Node Working Group database from 1994 to 2012 identified 1,250 patients who had an SLNB and thin melanomas (≤ 1 mm). Clinicopathologic characteristics were correlated with SLN status and outcome.
SLN metastases were detected in 65 (5.2%) of 1,250 patients. On univariable analysis, rates of Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, ulceration, and absence of regression differed significantly between positive and negative SLN groups (all P < .05). These four variables and mitotic rate were used in multivariable analysis, which demonstrated that Breslow thickness ≥ 0.75 mm (P = .03), Clark level ≥ IV (P = .05), and ulceration (P = .01) significantly predicted SLN metastasis with 6.3%, 7.0%, and 11.6% of the patients with these respective characteristics having SLN disease. Melanomas < 0.75 mm had positive SLN rates of < 5% regardless of Clark level and ulceration status. Median follow-up was 2.6 years. Melanoma-specific survival was significantly worse for patients with positive versus negative SLNs (P = .001).
Breslow thickness ≥ 0.75 mm, Clark level ≥ IV, and ulceration significantly predict SLN disease in thin melanoma. Most SLN metastases (86.2%) occur in melanomas ≥ 0.75 mm, with 6.3% of these patients having SLN disease, whereas in melanomas < 0.75 mm, SLN metastasis rates are < 5%. By using a 5% metastasis risk threshold, SLNB is indicated for melanomas ≥ 0.75 mm, but further study is needed to define indications for SLNB in melanomas < 0.75 mm.
Breast cancer remains a significant cause of death for women globally, despite advancements in detection and treatment, low‐ and middle‐income countries face unique obstacles. Role of Research ...Working Group (RWG) can expedite research progress by fostering collaboration between scientists, clinicians, and stakeholders. Benefits of a Global RWG include pooling resources and expertise to develop new research ideas, addressing disparities, and building local research capacity, with the potential to improve breast cancer research and outcomes.
Background Low false negative rates can be achieved with sentinel lymph node biopsy (SLNB) after neoadjuvant chemotherapy (NAC) in breast cancer (BC) patients with clinical N1 (cN1) disease. We ...examined changes in axillary management and oncologic outcomes in BC patients with cN1 disease receiving NAC. Methods BC patients with biopsy proven cN1 disease treated with NAC were selected from our institutional cancer registry (2014-2017). Patients were grouped by axillary management, axillary lymph node dissection (ALND), SLNB followed by ALND, or SLNB alone. Univariable and multivariable survival analysis for recurrence-free survival (RFS) and overall survival (OS) were performed. Results 81 patients met inclusion criteria: 31 (38%) underwent ALND, 25 (31%) SLNB + ALND, and 25 (31%) SLNB alone. A SLN was identified in 45/50 (90%) patients who had SLNB. ALND was performed in 25/50 (50%) patients who had SLNB: 18 for a + SLNB, 5 failed SLNB, and 2 insufficient SLNs. 25 patients had SLNB alone, 17 were SLN- and 8 SLN+. In the SLNB alone group, 23/25 (92%) patients received adjuvant radiation (RT). 20 (25%) patients developed BC recurrence: 14 distant (70%), 3 local (15%), 2 regional + distant (10%), and 1 contralateral (5%). In the SLNB alone group, there was 1 axillary recurrence in a patient with a negative SLNB who did not receive RT. Univariable survival analysis showed significant differences in RFS and OS between axillary management groups, ALND/SLNB + ALND vs. SLNB alone (RFS: p = 0.006, OS: p = 0.021). On multivariable survival analysis, worse RFS and OS were observed in patients with TNBC (RFS: HR 3.77, 95% CI 1.70-11.90, p = 0.023; OS: HR 8.10, 95% CI 1.84-35.60, p = 0.006). Conclusions SLNB alone and RT after NAC in BC patients with cN1 disease who have negative SLNs at surgery provides long-term regional disease control. This analysis provides support for the practice of axillary downstaging with NAC and SLNB alone. Keywords: Breast cancer, Neoadjuvant therapy, Axillary surgery, De-escalation of treatment, Sentinel lymph node biopsy
Accessory breast tissue is a rare aberration of normal breast development, that presents most commonly in the axilla. Similar to normal breast tissue, it can undergo physiologic and pathologic ...changes, including malignant transformation. We report a rare case of accessory breast cancer, treated with surgical resection and axillary reverse mapping (ARM), and review current literature focusing on management. We report a 68-year-old female with a history of left breast cancer treated with lumpectomy and axillary dissection, who later developed in-breast recurrence treated with re-lumpectomy and sentinel node biopsy which mapped at the contralateral (right) axilla, but was negative. Two years later screening imaging revealed right axillary tail focal asymmetry with two spiculated masses. Core biopsy showed invasive ductal carcinoma (IDC), and histologic examination of the biopsy could not determine whether this represents a new primary breast cancer or axillary metastasis from the contralateral site. She underwent lumpectomy of the two masses and sentinel node biopsy. During surgery, the masses were identified in the axilla itself, rather than the axillary tail. Final pathology revealed IDC, pT1N0(sn), and extensive ductal carcinoma
(DCIS). Due to positive margins, she underwent re-lumpectomy with ARM. Final pathology revealed residual DCIS with negative new margins. The patient was referred for adjuvant radiotherapy. Accessory axillary breast tissue can be confused with axillary tail tissue. It is necessary for the surgeon to distinguish between them by meticulous physical examination and radiologic evaluation, as resection of axillary breast tissue may warrant reverse lymphatic mapping for lymphedema prevention.
Interleukin-21 (IL-21), a member of the IL-2 cytokine family, has diverse regulatory effects on natural killer (NK), T, and B cells. In contrast to other cytokines that are usually immunostimulatory, ...IL-21 can induce apoptosis of murine B cells at specific activation-differentiation stages. This effect may be used for treatment of B-cell malignancies. Herein we report that diffuse large B-cell lymphoma (DLBCL) cell lines exhibit widespread expression of the IL-21 receptor (IL-21R) and that IL-21 stimulation leads to cell-cycle arrest and caspase-dependent apoptosis. IL-21 also induces apoptosis in de novo DLBCL primary tumors but does not affect viability of human healthy B cells. Furthermore, IL-21 promotes tumor regression and prolongs survival of mice harboring xenograft DLBCL tumors. The antilymphoma effects of this cytokine are dependent on a mechanism involving IL-21–activated signal transducer and activator of transcription 3 (STAT3) up-regulating expression of c-Myc. This up-regulation promotes a decrease in expression of antiapoptotic Bcl-2 and Bcl-XL proteins triggering cell death. Our results represent one of the first examples in which the STAT3–c-Myc signaling pathway, which can promote survival and oncogenesis, can induce apoptosis in neoplastic cells. Moreover, based on IL-21's potency in vitro and in animal models, our findings indicate that this cytokine should be examined in clinical studies of DLBCL.
The paradigm shift in cancer treatment from cytotoxic drugs to tumor targeted therapies poses new challenges, including optimization of dose and schedule based on a biologically effective dose, ...rather than the historical maximum tolerated dose. Optimal dosing is currently determined using concentrations of tyrosine kinase inhibitors in plasma as a surrogate for tumor concentrations. To examine this plasma-tumor relationship, we explored the association between lapatinib levels in tumor and plasma in mice and humans, and those effects on phosphorylation of human epidermal growth factor receptors (HER) in human tumors.
Mice bearing BT474 HER2+ human breast cancer xenografts were dosed once or twice daily (BID) with lapatinib. Drug concentrations were measured in blood, tumor, liver, and kidney. In a randomized phase I clinical trial, 28 treatment-naïve female patients with early stage HER2+ breast cancer received lapatinib 1000 or 1500 mg once daily (QD) or 500 mg BID before evaluating steady-state lapatinib levels in plasma and tumor.
In mice, lapatinib levels were 4-fold higher in tumor than blood with a 4-fold longer half-life. Tumor concentrations exceeded the in vitro IC90 (~ 900 nM or 500 ng/mL) for inhibition of HER2 phosphorylation throughout the 12-hour dosing interval. In patients, tumor levels were 6- and 10-fold higher with QD and BID dosing, respectively, compared to plasma trough levels. The relationship between tumor and plasma concentration was complex, indicating multiple determinants. HER receptor phosphorylation varied depending upon lapatinib tumor concentrations, suggestive of changes in the repertoire of HER homo- and heterodimers.
Plasma lapatinib concentrations underestimated tumor drug levels, suggesting that optimal dosing should be focused on the site of action to avoid to inappropriate dose escalation. Larger clinical trials are required to determine optimal dose and schedule to achieve tumor concentrations that maximally inhibit HER receptors.
NCT00359190.
Post mastectomy radiation (PMR) is usually recommended for T3 or N2 breast cancer (BC). The role of PMR for stage II BC with T1/T2 lesions remains controversial. The aim of this study was to assess ...the role of PMR in this subgroup of patients.
A retrospective analysis of a prospectively collected database of all stage II BC patients treated with mastectomy at our institution between the years 2005-2008 was performed. Demographics, disease-free survival rates were compared between the patients receiving radiation vs. those who were not irradiated.
Eighty-two patients underwent mastectomies for stage II disease with a T1/T2 lesion. Twenty-two of those (27%) received PMR. Loco regional recurrence (LRR) occurred only in the non -irradiated (NR) group. A Kaplan Meier analysis of time to LRR in the NR group was performed. Mean time to local failure was 78.9 months, 6% at 3 years and 13% at 5 years. The time to LRR was significantly lower in the estrogen receptor (ER) negative group compared to the ER positive group (64 vs. 82 months, p=0.029). LRR free rate at 5 years was 100% in low grade tumors vs. 53% in high grade tumors, (p=0.001). In a Cox regression multivariate analysis none of those factors maintained significance.
ER negative status, high grade and node negativity were associated with LRR. A prospective trial randomizing stage II BC patients with T1/T2 lesions, negative hormone receptors and high-grade tumors to PMR following mastectomy arm vs. no radiation arm is recommended.
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