Helena R. Chang

Younger women with breast carcinoma have a poorer prognosis than older women

It is controversial whether breast cancer in young women is more aggressive than in older women. This study was initiated to determine age‐associated outcome of women with breast carcinoma.

Cryoablation of early-stage breast cancer: Work-in-progress report of a multi-institutional trial

BackgroundWith recent improvements in breast imaging, our ability to identify small breast tumors has markedly improved, prompting significant interest in the use of ablation without surgical excision to treat early-stage breast cancer. We conducted a multi-institutional pilot safety study of cryoablation in the treatment of primary breast carcinomas.MethodsTwenty-nine patients with ultrasound-visible primary invasive breast cancer ≤2.0 cm were enrolled. Twenty-seven (93%) successfully underwent ultrasound-guided cryoablation with a tabletop argon gas-based cryoablation system with a double freeze/thaw cycle. Standard surgical resection was performed 1 to 4 weeks after cryoablation. Patients were monitored for complications, and pathology data were used to assess efficacy.ResultsCryoablation was successfully performed in an office-based setting with only local anesthesia. There were no complications to the procedure or postprocedural pain requiring narcotic pain medications. Cryoablation successfully destroyed 100% of cancers <1.0 cm. For tumors between 1.0 and 1.5 cm, this success rate was achieved only in patients with invasive ductal carcinoma without a significant ductal carcinoma-in-situ (DCIS) component. For unselected tumors >1.5 cm, cryoablation was not reliable with this technique. Patients with noncalcified DCIS were the cause of most cryoablation failures.ConclusionsCryoablation is a safe and well-tolerated office-based procedure for the ablation of early-stage breast cancer. At this time, cryoablation should be limited to patients with invasive ductal carcinoma ≤1.5 cm and with <25% DCIS in the core biopsy. A multicenter phase II clinical trial is planned.

Optimal surgical treatment of invasive lobular carcinoma of the breast

AbstractBackground: The roles of breast conservation and surgical evaluation of the contralateral breast in the treatment of lobular carcinoma of the breast remain unclear. The aim of this study was to compare local recurrence, 5-year survival, and incidence of contralateral breast cancer in women with lobular carcinoma to that in women with infiltrating ductal carcinoma. Methods: Women with infiltrating ductal carcinoma (IDC) and invasive lobular breast carcinoma (ILC) diagnosed during the years 1984 to 1994 were identified through a statewide tumor registry. The women were divided into groups based on their histology and treatment (breast conservation or modified radical mastectomy). The incidences of contralateral breast cancer, local recurrence, and 5-year survival were compared within each histologic group and treatment category. Results: During the period 1984 to 1994, 4886 women were diagnosed with invasive lobular or ductal breast carcinoma. Of these, 316 (6.5%) had infiltrating lobular cancer. The 5-year survival rates were 68% and 71% for ILC and IDC, respectively (p=0.5). The local recurrence rates were 2.8% and 4.3% for ILC treated with lumpectomy and axillary nodal dissection (LAND) and modified radical mastectomy (MRM), respectively, which were not significantly different from that obtained with IDC (LAND=2.5%, MRM=2.1%). The incidence of contralateral breast cancer during the period was 6.6% and 6.5% for ILC and IDC, respectively. Conclusions: Invasive lobular carcinoma can be safely treated with breast conservation with no difference in local recurrence or survival. In the absence of a suspicious finding on clinical or radiologic examination, routine contralateral breast intervention is not recommended.

Breast-cancer diagnosis with nipple fluid bFGF

Early diagnosis of breast cancer is the key to extending survival of breast-cancer patients. We found that the concentrations of nipple fluid bFGF (basic fibroblast growth factor) was significantly increased in breast-cancer patients compared with concentrations in controls (1717 ng/L [SD 706] vs 19 ng/L [19]; Students t test p=0.027). Measurement of bFGF in nipple fluid could be a useful diagnostic tool for breast cancer, and deserves further study.

Outcomes and factors impacting local recurrence of ductal carcinoma in situ

The optimal management of ductal carcinoma in situ (DCIS) remains controversial. Investigators have focused on identifying patients who are eligible for treatment by excision alone. A retrospective analysis of patients with DCIS treated by various modalities was conducted to compare outcomes and determine factors significant for local recurrence (LR).

Prognostic Analysis of Survival in Small Breast Cancers

BACKGROUND Routine axillary dissection in patients with invasive small breast cancer remains controversial. We previously reported a model for predicting nodal involvement in patients with T1a or T1b breast cancer that may guide the practice of selective nodal dissection. The objective of this study was to determine whether the prognosticators that predict nodal metastases also predict survival. STUDY DESIGN This study is a retrospective review of 2,153 women with small invasive breast cancer (< or = 1 cm) diagnosed between January 1984 and December 1995. Cases were identified from a statewide tumor registry, the Hospital Association of Rhode Island, and the tumor registry at Baystate Medical Center in Massachusetts. The impact on survival of patient age (< or = 40 versus > 40 years), nodal status (positive versus negative), tumor size (T1a versus T1b), and tumor grade (1 versus 2 or 3) were analyzed. Breast cancer-specific survival (BCSS) was analyzed using the Kaplan-Meier method and the proportional hazards regression method. RESULTS There were 388 patients with tumors 0.5 cm or less (T1a) and 1,765 with tumors 0.6-1.0 cm (T1b). Nodal status was known in 68% of cases (1,461 of 2,153), and tumor grade was recorded in 42% of cases (902 of 2,153). In univariate analysis, age, grade, and nodal status were significant in their association with BCSS. Tumor size did not influence BCSS among patients with small invasive tumors. Women older than 40 years had superior survival compared with younger women (93% versus 78% at 5 years; p = 0.01). Similarly, women with low grade (1) tumors did better than those with higher grade (2 or 3) tumors (98% versus 88% at 5 years; p = 0.03). The 5-year BCSS was 96% versus 78% for node-negative versus node-positive disease, and the 10-year BCSS was 91% versus 62% (p = 0.001). In the multivariate analysis, age and nodal status remained firmly associated with survival, although grade lost its significance. CONCLUSIONS Small tumor size does not affect survival. Although risk profiles for nodal involvement can be constructed to help guide the practice of selective axillary lymphadenectomy in patients with small invasive breast cancers, these factors cannot serve as a surrogate to nodal status in establishing patient prognosis. Nodal status remains the most powerful determinant of survival in breast cancer patients, even those with very small tumors.

Tumor-associated antigens recognized by human monoclonal antibodies

AbstractBackground: Nonhuman monoclonal antibodies (MoAbs) of desired specificities have been studied in cancer treatment and tumor targeting with minimal success. Attempts of using humanized chimeric antibodies have not improved significantly their clinical applications. We have engaged in the development of human MoAbs by incorporating the in vitro immunization protocols to the nodal lymphocytes of cancer patients. Three human MoAbs thus generated were found to be strongly reactive with various human malignancies. The antigens recognized by the three antibodies were selected for immunochemical and biochemical characterizations. Methods: The antigens investigated were AgSK1, PA 1-2 and PA 3-1. The patterns of each antigen expression in various human cancer cell lines were studied by the immunocytochemical staining technique. The expression of AgSK1 in association with cellular proliferation was examined by the flow cytometry analysis. In studying the biochemical natures of these antigens, their sensitivies toward various chemical and physical treatments were determined. The antigens that were shown to be proteins were subjected to SDS-PAGE and Western blot for estimations of molecular weights. Results: The AgSK1 was detected in 10 human carcinoma cell lines but in none of the melanoma cell lines. This suggests that SK1 may be an epithelial or carcinoma marker. The phenotypic expressions of AgSK1 were shown to be associated with proliferation of carcinoma cells. Biochemically AgSK1 was a sialophycoprotein with an estimated molecular weight of 42–44 kilodaltons (kDa). HuMAb PA1-2 demonstrated a unique staining pattern at both the cytoplasmic and intercellular interface. The stained filamentlike structures extending from cell to cell indicated that Ag PA1-2 might play a role in cellular interactions. Biochemically, Ag PA1-2 appeared to be an asialocarbohydrate. The Ag PA3-1 was a cytoplasmic glycoprotein expressed by all 13 cell lines. The estimated molecular weights of PA3-1 were 164, 104, and 40 kDa. Conclusions: Tumor-associated antigens recognized by the human MoAbs may be more relevant clinically than those recognized by the mouse immune system. Carcinoma-specific human MoAbs are desirable for cancer treatment and tumor localization.

ERBB2 mutation is associated with a worse prognosis in patients with CDH1 altered invasive lobular cancer of the breast.

E-cadherin (CDH1) is a glycoprotein that mediates adhesion between epithelial cells and also suppresses cancer invasion. Mutation or deletion of the CDH1 gene has been reported in 30–60% cases of invasive lobular carcinoma (ILC). However, little is known about genomic differences between ILC with and without a CDH1 alteration. Therefore, we analyzed whole genome sequencing data of 169 ILC cases from The Cancer Genome Atlas (TCGA) to address this deficiency. Our study shows that CDH1 gene was altered in 59.2% (100/169) of ILC. No significant difference was identified between CDH1-altered and -unaltered ILC cases for any of the examined demographic, clinical or pathologic characteristics, including histologic grade, tumor stage, lymph node metastases, or ER/PR/HER2 states. Seven recurrent mutations (PTEN, MUC16, ERBB2, FAT4, PCDHGA2, HERC1 and FLNC) and four chromosomal changes with recurrent copy number variation (CNV) (11q13, 17q12-21, 8p11 and 8q11) were found in ILC, which correlated with a positive or negative CDH1 alteration status, respectively. The prevalence of the most common breast cancer driver abnormalities including TP53 and PIK3CA mutations and MYC and ERBB2 amplifications showed no difference between the two groups. However, CDH1-altered ILC with an ERBB2 mutation shows a significantly worse prognosis compared to its counterparts without such a mutation. Our study suggests that CDH1-altered ILC patients with ERBB2 mutations may represent an actionable group of patients who could benefit from targeted breast cancer therapy.

Modified Radical Mastectomy and Simple Mastectomy

Abstract Introduction: The surgical techniques used in mastectomy are in constant evolution because of advancement in knowledge and the needs of patients. Methodology: Literature review of different types of mastectomy. Results: Halsted radical mastectomy (RM), the first effective surgery in treating breast cancer, was later modified by Patey, Madden, and others to preserve the pectoralis major muscle. Studies showed comparable survival outcomes between the two types of mastectomy. The modified radical mastectomy (MRM) became the standard treatment for women with stage I and II breast cancer in the 1970s. However, the axillary lymph node dissection (ALND), a part of modified radical mastectomy, was associated with significant side effects. Hence, the simple mastectomy (SM) was developed to spare the ALND and focus on treating the local disease only. Studies showed that survival after SM with or without radiation was comparable to those with RM. Recently, adjuvant systemic treatment has been shown to significantly improve disease-free and overall survival in patients with node-positive breast cancer, which requires nodal staging to guide therapy. Sentinel lymph node biopsy (SLNB) was invented to provide adequate pathologic nodal status in clinically negative axilla. Today, SM coupled with SLNB has largely replaced the MRM. Additional modifications to mastectomy by sparing the skin and the nipple areolar complex further increased its popularity. Discussion: The evolution of surgical treatment of breast cancer is governed by the principles of controlling the local disease and providing adequate pathology with minimal adverse effects. The validity of any new procedure requires confirmation.

Sarcoma and Lymphoma of the Breast

Sarcomas arise from mesodermal structures. Common morphologic appearance and similar clinical patterns characterize these connective tissue tumors. The etiology is unknown, and most soft tissue sarcomas arise de novo. Soft tissue sarcomas expand radially and spread along paths of least resistance. Most develop pseudocapsules that contain tumor cells and therefore cannot be shelled out, as the risk of local recurrence is very high. Sarcomas rarely metastasize to regional lymph nodes. Hematogenous spread is common and occurs early. Pulmonary metastasis is often the first site of disseminated disease. Local recurrence is associated with disseminated disease in one-third of patients. The most important prognostic factors are histologic grade and size of tumor.