Francisco Acevedo

Correlation between Ki67 and Histological Grade in Breast Cancer Patients Treated with Preoperative Chemotherapy

BACKGROUND AND AIM Breast cancer (BC) is a heterogeneous disease and cell proliferation markers may help to identify subtypes of clinical interest. We here analyzed the correlation between cell proliferation determined by Ki67 and HG in BC patients undergoing preoperative chemotherapy (PCT). MATERIALS AND METHODS We obtained clinical/pathological data from patients with invasive BC treated at our institution from 1999 until 2012. Expression of estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor type 2 (HER2) and Ki67 were determined by immuno-histochemistry (IHC). Clinicopathological subtypes were defined as: Luminal A, ER and/or PR positive, HER2 negative, HG 1 or 2; Luminal B, ER and/or PR positive, HER2 negative or positive and/or HG 3; triple negative (TN), ER, PR and HER2 negative independent of HG; HER2 positive, ER, PR negative and HER2 positive, independent of HG. By using Ki67, a value of 14% separated Luminal A and B tumors, independently of the histological grade. We analyzed correlations between Ki67 and HG, to define BC subtypes and their predictive value for response to PCT. RESULTS 1,560 BC patients were treated in the period, 147 receiving PCT (9.5%). Some 57 had sufficient clinicopathological information to be included in the study. Median age was 52 years (26-72), with 87.7% invasive ductal carcinomas (n=50). We performed IHC for Ki67 in 40 core biopsies and 50 surgical biopsies, 37 paired samples with Ki67 before and after chemotherapy being available. There was no significant correlation between Ki67 and HG (p=0.237), both categorizing patients into different subtypes. In most cases Ki67 decreased after PCT (65.8%). Only 3 patients had pathologic complete response (cPR). CONCLUSIONS In our experience we did not find associations between Ki67 and HG. Determination of clinicopathological luminal subtypes differs by using Ki67 or HG.

Complete pathological response to Imatinib mesylate in an extraintestinal gastrointestinal stromal tumor

INTRODUCTION Gastrointestinal stromal tumors (GIST) are the most frequent mesenchymal tumors of the digestive tract. Extraintestinal locations (EGIST) have been described showing similar pattern of immunohistochemical markers than GIST. Inhibitors of tyrosine kinases such as Imatinib or Sunitinib are the mainstay treatment in the management of advanced or metastatic GIST. Complete pathological response to these agents is an extremely rare event, especially in the case of EGIST due to its more aggressive behavior reported. PRESENTATION OF CASE Here we describe the case of a 61 years old woman, with an advanced GIST, who was operated after 10 months of Imatinib mesylate. The biopsy demonstrated the extra intestinal location of the tumor and a complete pathological response was confirmed. DISCUSSION Complete pathological response to Imatinib is a rare event. To our knowledge, this is the first report of complete response in an EGIST. New clinical, radiological and metabolic criteria of tumoral response to neoadjuvant treatment are revised. CONCLUSION EGIST complete pathological response to Imatinib can be achieved. However, recommendation of systematic neoadjuvant therapy with Imatinib remains investigational and more studies are warranted in the future.

Breast cancer and pregnancy: a comparative analysis of a Chilean cohort

Introduction Recent reports show that pregnancy-associated breast cancer (PABC) survival is similar to that of non-pregnant young patients. We evaluate the characteristics and prognosis of PABC patients treated in our cancer centre. Patients and methods We identified patients with invasive PABC who were treated between 1999 and May 2013 and compared their characteristics with a no PABC cohort of similar age. Results The prevalence of PABC was 1% (n = 17). The median age was 35 years (range: 29– 42 years). The initial tumour was suspected clinically in 93% of the cases. Total mastectomy rates were higher in women with PABC (78.6% versus 40.5%, p = 0.02), and more tumours in the PABC group were triple negative, epidermal growth factor type 2 (HER2)–positive, and at advanced stages; however, these differences were not statistically significant. While estimated overall survival at ten years was higher in the non-PABC group (75.5% versus 80.5%, p = 0.043), disease-specific survival (DSS) rate at ten years was not statistically different between groups (83.9% for PABC and 75.5% for unrelated pregnancy BC, p = 0.37). Conclusions PABC is a rare event. In our cohort, it tended to be more aggressive. Compared with a similar age cohort, the DSS was not worse.

How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. Methods: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. Results: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. Conclusion: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC.

Terapia endocrina neoadyuvante en cáncer de mama, una alternativa de tratamiento e investigación

Neoadjuvant chemotherapy is an accepted strategy for patients with locally advanced breast cáncer. This approach increases the possibilities of conservative treatment and improves the resectability rates of initially unresectable tumors. In addition, preoperative systemic therapy allows the evaluation of prognostic and predictive factors, dynamically and in vivo. Since over 80% of these tumors express estrogen receptors (ER), endocrine therapy seems a logical treatment to employ in the neoadjuvant setting. The advent of new drugs that regúlate the ER function, along with the results of several clinical studies with the use of neoadjuvant endocrine therapy, support the feasibility and safety of utilizing this strategy before surgery. We herein analyze the available clinical evidence about the use of neoadjuvant therapy aiming to regúlate the activity of the ER. We also discuss the valué of predictive factors that could help the oncologist to select those patients most likely to benefit from this approach and the role of endocrine therapy as a research instrument.

Thymoma associated with hypogammaglobulinaemia and pure red cell aplasia

Thymomas are neoplasias that begin in the thymus and develop in the anterior mediastinum. They are commonly associated with a variety of systemic and autoimmune disorders, such as pure red cell aplasia, hypogammaglobulinaemia, pancytopaenia, collagen diseases, and, most commonly, myasthenia gravis. The presence of inter-current infections, especially diarrhoea and pneumonia, in the presence of lymphocyte B depletion and hypogammaglobulinaemia is known as Good’s syndrome and may affect up to 5% of patients with thymoma. While anaemia is present in 50%–86% of patients with Good’s syndrome, only 41.9% of cases present pure red cell aplasia. Concomitance of these two conditions has only been rarely studied. We report on the case of a 55-year-old man diagnosed with advanced thymoma, who, during the progression of his disease, developed signs and symptoms suggesting Good’s syndrome and pure red cell aplasia. We also performed a brief review of the literature concerning this association, its clinical characteristics, and treatment.

Radiation recall dermatitis: report of two cases

Systemic treatment for cancer including chemotherapy or biologic agents can cause different changes in the skin or mucous membranes. These changes may represent a known adverse reaction to these drugs, although other etiologies should be considered. One of these, radiation recall dermatitis, is a rare and unpredictable phenomenon. Herein, we report two cases of this condition in women with metastatic breast cancer secondary to gemcitabine and the combination of capecitabine and ixabepilone.

Actividad física y cáncer de mama: un tratamiento dirigido

In Chile breast cancer (BC) is the first cause of death in women. While the most important risk factor for its development is estrogenic stimulation, environmental factors and lifestyles also contribute to its pathogenesis. Epidemiological studies show a direct relationship between physical activity (PA), incidence and recurrence of BC. Supervised PA practice is recommended in most cancer patients to improve their quality of life, to reduce adverse effects from treatment and eventually to improve the prognosis of the disease. We review the epidemiological evidence linking PA and BC and the biological basis of this relationship. We also review the relevant interventional studies and we explore some practical indications of PA in patients with BC, as a model for other tumors of epidemiological importance.

Evaluación del valor pronóstico de la relación neutrófilos/linfocitos en cáncer de mama de subtipos agresivos

Background: The white blood cell count is one of the most sensitive markers associated with inflammation. The neutrophil/lymphocyte count ratio may be an independent factor for breast cancer mortality. Aim: To assess the predictive value of the neutrophil/lymphocyte ratio for mortality in breast cancer. Material and methods: Review of the database of a cancer center of a University hospital. Patients with infiltrating breast cancer treated between 1997 and 2012 were selected. The pathology type and lymph node involvement were obtained from the pathology report. The expression of estrogen, progesterone and Human Epidermal Growth Factor Receptor 2 (HER2) was determined by immunohistochemistry or in situ fluorescent hybridization (FISH). The absolute peripheral neutrophil and lymphocyte counts were obtained from a complete blood count obtained at least three months before treatment. Patients were followed for a median of 61 months (range 1-171). Results: From 323 eligible patients, after excluding those in stage IV and those without an available complete blood count, 131 patients were analyzed (81 with negative receptors and 117 HER2 enriched). The neutrophil/lymphocyte ratio was similar in both type of tumors (2.1 and 1.91 respectively). Twenty two patients died during follow up. Surviving patients with HER2 enriched tumors had a lower neutrophil/lymphocyte ratio than those who died (1.79 and 3.21 respectively, p < 0.01). In a multivariate analysis, including age, tumor stage and lymph node involvement as confounding factors, the neutrophil/lymphocyte ratio was still significantly associated with a risk of death with a hazard ratio of 2.56. Conclusions: A high neutrophil/lymphocyte ratio in the complete blood count can be a predictor of death in breast cancer.

Breast Cancer at Extreme Ages - a Comparative Analysis in Chile

BACKGROUND Young onset breast cancer (BC) has a worse outcome as compared to in the elderly. However, some studies have shown that BC in the elderly, despite indolent features, does also cause increase in mortality. In an attempt to compare clinic-pathological characteristics, BC subtypes and survival in patients with BC presenting at extremes of age, we performed a retrospective study. MATERIALS AND METHODS Patients were either ≤40 or ≥70 years old. Subtypes were defined using immunohistochemistry and histological grade. Chi-Square test was used for evaluation of categorical variables, and Kaplan-meier and log-rank for disease-specific survival (DSS) and disease free survival (DFS) . RESULTS We analyzed 256 patients ≤40 and 366 patients ≥70. Younger patients presented with more aggressive disease, with less luminal A but more luminal B and triple negative (TN) subtype. With a median follow-up of 57.5 months, DFS at 5 years in younger patients was 72.3% vs 84.6% in the elderly (p=0.007). Luminal A and B disease presented with worse DFS in younger patients. The opposite was seen in the TN subgroup. Although we found no significant differences in DSS, older patients with TN tumors died of BC more frequently. This group also received less chemotherapy. CONCLUSIONS Young patients present with more aggressive disease, this translating into worse DFS. However, elderly patients with TN disease represent a particular subpopulation with worse DFS and DSS, suggesting that chemotherapy should not be withheld only because of age.