Hormone receptor positive tumors represent the most common form of breast cancer and account for most of the deaths from the disease. Endocrine therapy represents the main initial therapeutic strategy for these patients and has been associated with significant clinical benefits in a majority of patients. While in early stages endocrine therapy is administered as part of a curative approach once clinical metastases develop, the disease is considered incurable and the main management objectives are tumor control and quality of life. The two major clinical paradigms of always indicating endocrine therapy in the absence of visceral crises and sequencing endocrine treatments have been guiding our therapeutic approach to these patients. However, for many decades, we have delivered endocrine therapy with a ‘one size fits all’ approach by applying agents that interfere with hormone receptor signaling equally in every clinical patient scenario. We have been unable to incorporate the well-known biologic principle of different degrees of hormone receptor dependency in our therapeutic recommendations. Recent developments in the understanding of molecular interactions of hormone signaling with other important growth factor, metabolic and cell division pathways have opened the possibility of improving results by modulating hormone signaling and interfering with resistance mechanisms yet to be fully understood. Unfortunately, limitations in the design of trials conducted in this area have made it difficult to develop predictive biomarkers and most of the new combinations with targeted agents, even though showing improvements in clinical endpoints, have been directed to an unselected population of patients. In this review we explore some of the current and most relevant literature in the management of hormone receptor positive advance breast cancer.

Bleomycin is a chemotherapeutic agent commonly used to treat curable diseases such as germinative tumors and Hodgkin’s lymphoma. The major limitation of bleomycin therapy is pulmonary toxicity, which can be life threatening in up to 10% of patients receiving the drug. The mechanism of bleomycin-induced pneumonitis (BIP) involves oxidative damage, relative deficiency of the deactivating enzyme bleomycin hydrolase, genetic susceptibility, and the elaboration of inflammatory cytokines. Ultimately, BIP can progress to lung fibrosis. The diagnosis of BIP is established by the combination of systemic symptoms, radiological and histological findings, and respiratory function tests abnormalities, while other disorders should be excluded. Although the diagnosis and pathophysiology of this disease have been better characterized over the past few years, there is no effective therapy for the disease. In general, the clinical picture is extremely complex. A greater understanding of the BIP pathogenesis may lead to the development of new agents capable of preventing or even treating the injury already present. Physicians who prescribe bleomycin must be aware of the potential pulmonary toxicity, especially in the presence of risk factors. This review will focus on BIP, mainly regarding recent advances and perspectives in diagnosis and treatment.

Hormone receptor (HR) positive breast cancer is the most frequent breast cancer subtype. Endocrine therapy targeting the estrogen receptor (ER) pathway represents the main initial therapeutic approach. The major strategies include estrogen deprivation and the use of selective estrogen modulators or degraders; which show efficacy in the management of metastatic and early stage disease. However, clinical resistance associated with progression of disease remains a significant therapeutic challenge. Mutations of the ESR1 gene, which encodes the ER, have been increasingly recognized as an important mechanism of endocrine therapy resistance, with a prevalence that ranges from 11 to 39%. The majority of these mutations are located within the ligand-binding domain and result in an estrogen-independent constitutive activation of the ER and therefore resistance to estrogen deprivation therapy such as aromatase inhibition. ESR1 mutations, most often detected from liquid biopsies, have been consistently associated with a worse outcome and are being currently evaluated as a potential biomarker to guide therapeutic decisions. At the same time, targeted therapy directed to ESR1-mutated clones is an appealing concept with preclinical and clinical work in progress.

Breast cancer is a heterogeneous disease, and the estrogen receptor (ER) remains the most important biomarker in breast oncology. Most guidelines set a positive expression threshold of 1% staining in immunohistochemistry (IHC) to define ER positivity. However, different expression levels may be associated with diverse degrees of sensitivity to endocrine therapy as ER expression may impact breast cancer molecular biology as a continuous variable. ER^-lo tumors, defined as those with 1-10% ER expression, represent a relatively small subgroup of breast cancer patients, with an estimated prevalence of 2-7%. These tumors are similar to ER^neg disease in their molecular landscape, clinicopathological characteristics, prognosis, and response to therapy. Nevertheless, a proportion may retain some degree of ER signaling dependency, and the possibility of responding to some degree to endocrine therapy cannot be completely ruled out. This review article discusses the most important considerations regarding the definition of ER positivity, pathology assessment, prognosis, and therapeutic implication of ER^lo breast cancer from the medical oncology perspective.

Purpose: Patients with human epidermal growth factor receptor 2 (HER2) -positive metastatic tumors treated in the public health system in Brazil do not have access to trastuzumab. This study aimed to estimate the impact of the lack of access to anti-HER2 therapies on the mortality of these patients. Methods: On the basis of published data, the number of patients with HER2-positive advanced breast cancer in 2016 who should receive anti-HER2 targeted therapy was estimated. Three different treatment groups were considered for this hypothetical cohort: chemotherapy alone, chemotherapy plus trastuzumab, and chemotherapy plus trastuzumab and pertuzumab. The number of patients alive after 2 years of follow-up was estimated on the basis of the efficacy results of the pivotal trials considering these interventions. Results: It was calculated that 2,008 women will be diagnosed with advanced HER2-positive breast cancer in Brazil in 2016. It was estimated that only 808 women would be alive in 2018 if they receive only chemotherapy (which is the treatment offered by the public health system). On the other hand, the bar rises to 1,408 women alive in 2018 if they receive chemotherapy plus trastuzumab and 1,576 women alive in 2018 if they receive the gold standard of chemotherapy plus trastuzumab and pertuzumab. Conclusion: Trastuzumab is included in the WHO’s list of essential medications, but the Brazilian public health system does not yet provide this treatment to its population with advanced disease. The introduction of trastuzumab and pertuzumab would have a positive effect, preventing premature deaths in women with metastatic HER2-positive breast cancer in Brazil.