Fetal Renal Insufficiency Following Trastuzumab Treatment for Breast Cancer in Pregnancy: Case Report und Review of the Current Literature

Some drugs are known for their fetal nephrotoxicity and should be avoided during pregnancy. We report on a pregnant woman suffering from breast cancer who received a weekly neoadjuvant trastuzumab (Herceptin^®) therapy from 15 weeks of gestation onward, in addition to a 3-weekly carboplatin/docetaxel chemotherapy. Fetal renal insufficiency with anhydramnios and missing visualization of the fetal bladder developed at 21 weeks. After discontinuation of trastuzumab and repeated instillation of amniotic fluid, the amount of amniotic fluid remained stable after 24 weeks of gestation. After caesarean section at 34 weeks because of fetal growth restriction, the renal function of the neonate was normal postnatally. In accordance with the current literature, our case shows a reversible adverse effect of trastuzumab on the fetal renal function and confirms the current recommendation that trastuzumab in pregnancy should be avoided. In pregnancies exposed to trastuzumab, treatment should be discontinued and the fetus should be closely monitored, with particular attention to the amniotic fluid and the fetal bladder volume, as these reflect fetal renal function.     

Long-Term Disease Control with Lapatinib and Capecitabine in a Heavily Pretreated Patient with ErbB2-Positive Metastatic Breast Cancer

BACKGROUND: The optimal sequence of systemic palliative chemotherapy in metastatic breast cancer is unknown. CASE REPORT: We report the course of disease in a patient aged 24 years at the onset of disease, who was treated over 17 years for her metastatic ErbB2-positive breast cancer. Seventeen years ago, the patient was diagnosed to have invasive ductal breast cancer and underwent surgical treatment. She received 6 cycles of adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate, 5-fluorouracil). Twenty-eight months after the primary surgery, the patient developed a histologically verified lung metastasis, and subsequently received 8 different lines of chemotherapy, including high-dose cytotoxic therapy and stem cell support as well as trastu-zumab. In addition, she received 5 different types of antihormonal treatment. Due to the recent progression of her lung metastasis, 27 cycles of lapatinib and capecitabine were administered. A long-term partial response in the lung was observed. CONCLUSIONS: Individualized systemic treatment with the tyrosine kinase inhibitor lapatinib and capecitabine in heavily pretreated patients with Her2-positive metastatic breast cancer may lead to effective palliation for almost 2 years despite extensive pretreatment.     

Investigating the Combination of Trastuzumab and HER2/neu Peptide Vaccines for the Treatment of Breast Cancer

Background Trastuzumab, an anti-HER2/neu monoclonal antibody, is thought to promote HER2/neu receptor internalization and/or turnover. This study was designed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte–mediated lysis. Methods Three cell lines with varying levels of HER2/neu expression were incubated with varying doses of trastuzumab at multiple time points. Trastuzumab binding and HER2/neu expression were determined. Peripheral blood mononuclear cells from three HLA-A2⁺ healthy donors and four E75 peptide–vaccinated patients were stimulated with HER2/neu-derived peptides and tested in standard chromium release cytotoxicity assays with HER2/neu⁺ tumor cells pretreated with trastuzumab. Results Treatment of tumor cells with 10 μg/mL of trastuzumab in an overnight incubation resulted in saturation of cell-surface HER2/neu receptors. At higher doses, trastuzumab staining and HER2/neu expression decreased in a time-dependent manner. Pretreatment of tumor cells with trastuzumab resulted in increases in specific cytotoxicity by peptide-stimulated cytotoxic T lymphocytes from HLA-A2⁺ donors over untreated cells by an average of 5.6% and 15.3% (P = .0002) for doses of 10 and 50 μg/mL, respectively. In similar experiments involving peripheral blood mononuclear cells obtained from immunized patients, the average specific cytotoxicity for untreated cells was 34.2% ± 1.3% vs. 40.6% ± 2.5% (P = .035) and 40.7% ± 1.6% (P = .0005) for those treated with 10 and 50 μg/mL, respectively. Conclusions Our data suggest that pretreatment of breast cancer cells with trastuzumab induces turnover of the HER2/neu protein and enhanced killing by HER2/neu peptide–stimulated CTLs. This increased lysis occurs regardless of the degree of HER2/neu expression and seems more pronounced in vaccinated patients. These findings support further investigation into the use of combination immunotherapy with trastuzumab and HER2/neu peptide–based vaccines. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army or the Department of Defense.     

Adopting Guidelines into Clinical Practice: Implementation of Trastuzumab in the Adjuvant Treatment of Breast Cancer in Lower Saxony, Germany, in 2007

SUMMARY: BACKGROUND: Few studies have assessed the quality of medical care in breast cancer patients outside clinical studies and certified centres in German-speaking countries. We used ONkeyLINE, a voluntary tumour registry, to evaluate the rate of adoption into clinical practice of guidelines on the adjuvant use of trastuzumab and to estimate the reliability of ONkeyLINE in assessing quality of care. MATERIAL AND METHODS: Data from ONkeyLINE were analysed to answer questions on the quality of breast cancer care in daily practice in 2007. The influence of age and area (rural/urban) on treatment patterns was also evaluated. RESULTS: Data from approximately 85% of patients diagnosed with breast cancer in Lower Saxony in 2007 were documented in ONkeyLINE. Within 1 year, more than 77% of patients received adjuvant trastuzumab according to the updated guidelines. Variations in chemotherapy and trastuzumab according to age were evident, in part but not fully attributable to comorbidities in the elderly. Access to trastuzumab therapy in rural areas was as high as in urban areas. CONCLUSIONS: Adoption of national guidelines into clinical practice was observed at a reasonable but still unsatisfactory rate in Lower Saxony. Although voluntary, ONkeyLINE covered most breast cancer cases and proved to be a reliable tool for assessing quality of care.     

Modeling Metastatic Breast Cancer in Mice

Metastatic disease is the major cause of death in breast cancer patients. Patients presenting with metastases cannot be cured, and as a consequence, treatment is palliative and focuses on prolonging survival and maintaining quality of life. Numerous mouse models have been generated in which human breast cancer development and metastasis have been studied, ranging from spontaneous and carcinogen-induced models to transplantation models and genetically engineered mouse models. Here, we summarize past progress and highlight present developments in modeling breast cancer invasion and metastasis in genetically modified mice, and the impact it may have on the development of innovative anticancer therapies.     

乳腺癌前哨淋巴结活检的研究进展

目的 报道乳腺癌前哨淋巴结活检的研究进展。方法 采用文献回顾的方法，对国外乳腺癌前哨淋巴结活检的历史、概念、活检技术以及临床应用等问题进行综述。结果 乳腺癌前哨淋巴结活检的操作方法还没有统一的标准，检出率及假阴性率变化范围广。结论 前哨淋巴结活检的临床应用还需要大量前瞻性多中心随机实验结果进一步论证。     

Parotid Gland Metastasis of Breast Cancer: Case Report and Review of the Literature

BACKGROUND: Parotid gland metastasis in breast cancer is extremely rare, and only 14 cases have been reported between 1982 and 2010. CASE REPORT: A 67-year-old female patient was diagnosed with invasive lobular carcinoma of the left breast. Although clinical staging was T1N3M1 (stage IV), the tumor experienced a complete response to chemotherapy. We therefore performed a mastectomy followed by radiotherapy, and continued administration of trastuzumab. However, 11 months later, the patient complained of a swelling in the left parotid gland. Histology following a partial parotidectomy revealed a parotid gland metastasis from the breast. CONCLUSION: Treatment with capecitabine in addition to trastuzumab, which is one of the strategies applied in HER2-positive breast cancer, was effective in our patient. Analysis of the 14 cases of parotid gland metastasis from the breast reported between 1982 and 2010 revealed that the metastasis may occur not by direct lymphatic but by hematogenous spread.     

A Giant Mammary Hamartoma in a Young Breast Cancer Patient

BackgroundHamartomas of the breast are rare benign tumors. Pre- and also postoperative differentiation from other benign or even malignant tumors is challenging.Case PresentationA 36-year-old female presented with a giant tumor of the left breast. The patient had suffered from an early breast cancer of the contralateral right breast the year before, which was treated with breast-conserving therapy, radiation, and endocrine therapy ever since. The hamartoma was classified as BI-RADS 2 in mammography and BI-RADS 4 in ultrasound. On clinical examination, a tumor of nearly 15 cm in size led to an abstruse deformity of the breast and the nipple-areola complex. We found an indolent, grand bulging tumor with an elastic texture directly beneath the skin. A biopsy that had been performed before was compatible with the suspected hamartoma. Because of the remaining diagnostic uncertainties after contralateral breast cancer and the progressive malformation of the left breast, a tumor extirpation utilizing a reduction mammaplasty was performed without complications. Subsequent genetic analyses excluded a loss of PTEN in this patient.ConclusionWe presented the rare case of a 36-year-old woman with a history of breast cancer and a 700-g breast hamartoma. The preoperative and even the postoperative specification of a hamartoma remains challenging, and associations with genetic alterations should be considered.     

尿多酸肽对乳腺癌细胞周期的影响

目的研究肿瘤细胞分化诱导剂尿多酸肽（CDA-Ⅱ）对乳腺癌细胞周期的影响。方法将CDA-Ⅱ与乳腺癌细胞株MCF-7和MDA-MB-231进行体外培养，同时以维甲酸为阳性对照，观察其对乳腺癌细胞生长曲线、细胞周期、形态学等方面的影响。结果CDA-Ⅱ可减缓两株乳腺癌细胞的生长和增殖能力，使乳腺癌细胞的细胞周期的分布出现S期比例减少，G0／G1期增加。结论CDA-11可抑制不同生物学特性的两株乳腺癌细胞的生长和增殖能力，细胞周期出现G0／G1期阻滞，为CDA-Ⅱ治疗乳腺癌提供了实验依据。     

乳腺癌保乳手术中乳房缺损的修复方法

目的综述乳腺癌保乳手术中乳房缺损的修复方法。方法分析近年来相关文献,对有关乳腺癌保乳手术中乳房缺损的修复方法、适应证、切口选择以及优缺点进行分析。结果保乳手术后部分患者存在乳房畸形,美容效果不佳。如何选择手术切口、怎样修复肿瘤切除后的乳房缺损,以获得较好的美容效果是外科手术中的焦点问题。将乳房整形技术应用于保乳手术,可明显改善美容效果。结论选择合适的早期乳腺癌患者采用乳房整形技术进行保乳手术治疗,安全、有效,术后患者对乳房外形及整体美容效果满意度高,是值得推荐的一种技术。     

Treatment of Recurrent Breast Cancer Following Breast Conserving Surgery

Patients with isolated ipsilateral breast cancer recurrence face completion mastectomy in the majority of cases. Selected patients may derive good outcomes from repeat breast conservation surgery and indeed repeat irradiation may be employed using one of many different modalities. Tumor biology rather than salvage surgery method is likely to influence outcome. Patients with isolated breast tumor recurrence are treated in the majority of cases with completion mastectomy, when for selected patients there exists little evidence that more radical surgery provides better outcomes in terms of further recurrence and overall survival, than repeated breast conserving surgery. Literature search identifying articles addressing the issue of repeat breast conserving surgery for ipsilateral breast tumor recurrence, and repeat radiotherapy (search terms include: repeat breast conserving surgery, salvage mastectomy, salvage breast conserving surgery, salvage radiotherapy, reirradiation). Thirty‐five articles discussed the outcomes of repeat breast conserving surgery versus salvage mastectomy, methods of repeat breast irradiation, repeat sentinel lymph node biopsy and related factors. Repeat breast conserving surgery may represent a safe and feasible treatment method for isolated ipsilateral breast tumor recurrence.     

Trastuzumab combined to neoadjuvant chemotherapy in patients with HER2-positive breast cancer: a systematic review and meta-analysis

Purpose

To perform a meta-analysis in order to quantify the actual cumulative randomized evidence for the benefit and toxicity of trastuzumab combined with neoadjuvant chemotherapy in HER2-positive breast cancer.

Methods

Potentially eligible trials were located through PubMed and Cochrane Library searches and abstracts of major international conferences. The endpoints that we assessed were pathologic complete response (pCR) rate, breast-conserving surgery (BCS) rate and toxicity.

Results

Five trials were identified with 515 eligible patients. The probability to achieve pCR was higher for the trastuzumab plus chemotherapy arm (RR 1.85, 95% CI: 1.39–2.46; p-value < 0.001). No significant difference in terms of breast-conserving surgery between the two treatment arms was observed (OR: 0.98, 95% CI: 0.80–1.19, p-value = 0.82). Regarding toxicity, the addition of trastuzumab did not increase the incidence of neutropenia, neutropenic fever, and cardiac adverse events.

Conclusion

The addition of trastuzumab in HER2-positive breast cancer in the neoadjuvant setting improves the probability of achieving higher pCR with no additional toxicity. Based on the available evidence, the use of trastuzumab combined with neoadjuvant chemothetherapy in patients with HER2-positive breast cancer seems to offer substantial benefit in terms of pCR.     

Primary Cutaneous Angiosarcoma of the Scalp with Cranial Invasion in a Patient with Metastatic Breast Cancer

Idiopathic cutaneous angiosarcoma (CA) of the head and neck is a distinct subtype of angiosarcoma most commonly presenting as a single or multiple purple, bruise-like patches that arise de novo and enlarge over several months. In clinical practice, both misdiagnosis and delayed diagnosis are frequently encountered. Here, we present a case of idiopathic CA on the scalp with invasion to the cranium in a patient with breast cancer metastatic to the brain. The patient was initially misdiagnosed and mistreated with herpes zoster and breast cancer metastatic to the skin, which led to a delayed diagnosis by two months until dermatologic evaluation. The diagnosis was then firmly established as CA based on consistent clinical and histological features. Since the tumor was inoperable, radiotherapy and chemotherapy were been considered as the appropriate adjuvant modes of therapy. Despite an initial favorable response, the disease demonstrated a rapidly progressive course and the patient succumbed to the disease within six months. This report briefly reviews the clinical and histological portrait and management options for this aggressive tumor.     

Breast Cancer Following Augmentation Mammaplasty with Polyacrylamide Hydrogel (PAAG) Injection

Polyacrylamide hydrogel (PAAG) as an implanted material for augmentation mammaplasty has been used for years in China. Many kinds of complications associated with PAAG use have been reported in the clinical literature. This report presents two cases of breast cancer occurring after injection of PAAG in augmented breasts. The delayed diagnosis and more aggressive disease due to PAAG injection should be cause for concern. It is very important to detect breast cancer early when it is covered by the induration of the injected gel and inflammation reaction after PAAG injection. PAAG injection for augmentation mammaplasty may affect the outcome of breast cancer diagnosis and prognosis.     

The Role of Sentinel Lymph Node Biopsy with Blue Dye Alone in Breast Cancer Patients with Excisional Biopsy

Purpose : Sentinel lymph node biopsy (SLNB) appears to offer an excellent alternative method to routine axillary lymph node dissection for staging patients with breast cancer. The aim of this study is to evaluate the effect of excisional biopsy on identification and false negative rate of sentinel lymph node biopsy with blue dye alone in breast cancer patients with clinically negative axilla.

Material and Methods : From March 1998 to March 2003, 266 consecutive sentinel lymph node biopsies (SLNB) were performed using isosulfan blue dye alone. Patients were divided into two groups. One hundred and four patients (39.1%) had previously undergone an excisional biopsy (Group I); in 162 patients (60.9%), pre-operative diagnosis was obtained by either fine-needle aspiration biopsy (FNAB) or core biopsy (Group II). Following sentinel lymph node biopsy, all patients had axillary lymph node dissection (ALND). Data concerning patients, sentinel lymph nodes and the status of the axilla were collected and compared using Fisher’s exact test. A p value of less than 0.05 was considered statistically significant.

Results : The sentinel lymph node was successfully identified by blue dye in 94.3% (251/266) of patients. Mean lymph nodes removed from the axilla was 19 (range 11–36) and the mean number of sentinel nodes was 2 (range 1–5). The identification and false negative rate were unrelated to size, type or location of the tumour, or a previous surgical biopsy. Conclusions : SLNB with blue dye for evaluation of the axilla is a rapid and accurate technique that provides increased efficacy in the detection of lymphatic metastasis when careful pathologic evaluation with serial sections is performed. The risk-benefit analysis of lymphatic mapping with blue dye provides improvement in staging, with reduced morbidity and hospital stay, and the elimination of general anaesthesia. The technique may also be used safely and accurately in breast cancer patients with excisional biopsy.     

Influence of Family History of Breast or Ovarian Cancer on Pathological Complete Response and Long-Term Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

PurposeIn breast cancer, a pathological complete response (pCR) has been described as generally resulting in a favorable prognosis. However, there are subgroups, such as patients with a mutation in BRCA1 or BRCA2, in which the effect of pCR on the prognosis is suspected to be weaker. Patients with a family history of breast and/or ovarian cancer may therefore react differently in relation to pCR and prognosis, and this is investigated in this study.Patients and MethodsBreast cancer patients were identified from a clinical breast cancer registry. The study subjects had been treated with neoadjuvant chemotherapy from 2001 to 2018 and their pathological and clinical information as well as medical family history were available. They were considered to have a positive family history if they had at least 1 first-degree relative with breast and/or ovarian cancer. Multivariate logistic regression analyses were performed to study the association between family history, pCR (ypT0; ypN0), and disease-free survival (DFS).ResultsOf 1,480 patients, 228 (15.4%) had a positive family history. The pCR rates were 24.9% in all patients, and 24.4% and 27.6% in those without/with a family history, respectively. Family history was not associated with a higher pCR rate (adjusted odds ratio [OR] 1.23; 95% confidence interval [CI] 0.85–1.76; p = 0.27) or a different disease-free survival (DFS; adjusted hazard ratio [HR] 1.15; 95% CI 0.88–1.52; p = 0.30). pCR did not affect the prognosis differently in relation to family history.ConclusionsIn this retrospective analysis, family history was not associated with pCR and DFS. pCR improved survival, independently of family history.