Reviews 4th Stage Metastic Breast Cancer Treatment in Mexico

INTRODUCTION

Section:

At the beginning of the century, Mexico faced several issues that severely hampered the health care arrangement's ability to provide services for the entire population: low government spending in health, a predominance of out-of-pocket expenses, an diff distribution of public resources between social security schemes, and a failing health infrastructure.¹ Until 2003, Mexicans who were non covered by social security (those without a formal employer) or without private insurance were not entitled to any benefits or wellness care plans and faced a high gamble of catastrophic expenditure, which affected more than half of the Mexican population.²

In 2001 to 2006, the Programa Nacional de Salud (National Wellness Program) established the Seguro Popular de Salud (Popular Wellness Insurance), which aimed to extend health care coverage to the entire Mexican population.³ In Apr 2003, a reform to the Ley General de Salud (Full general Wellness Constabulary) was approved, leading to the creation of the Sistema de Proteccion Social en Salud (System of Social Protection in Health) and making universal health coverage mandatory from a legal standpoint.^four These deportment intended to promote a reduction in the catastrophic health spending incurred by families and to create a health care organisation that incentivized efficient spending and equitable and attainable medical intendance. In add-on to offer attending for multiple primary care–level health problems, the Organisation of Social Protection in Health covers several expensive specialized diseases and interventions through the Fondo de Proteccion contra Gastos Catastroficos (Catastrophic Expenses Protection Fund, FPGC). The FPGC is funded with contributions from three sources: federal authorities, state governments, and beneficiary families, who contribute according to their income. These resources are managed through a federal trust, which reimburses providers (both public and private) who offer health care for the diseases included in the FPGC, using fixed rates for each intervention.⁵

The diseases and interventions included in the FPGC were chosen by members from the National Wellness Council, who selected those diseases that were prevalent and probable to crusade catastrophic expenses. In 2004, merely 90 interventions and four diseases were covered (HIV/AIDS, cervical cancer, lymphoblastic leukemia in children, and cataracts), and 5.3 1000000 people were affiliated. By 2013, the number of covered interventions had increased to 285, and the number of affiliated individuals to 57.3 million.⁶ Because of its rising incidence in Mexico, breast cancer was included in FPGC's covered diseases in 2007, and it currently receives upward to 25% of its budget.^7-9 One of the master consequences of its inclusion has been the reduction in loss to follow-up of patients with breast cancer, which went from 30% earlier 2007 to less than 6%.^x

Here we depict the clinical characteristics, prognostic factors, and outcomes of patients with chest cancer treated at the Instituto Nacional de Cancerologia (National Cancer Institute, INCan) of Mexico betwixt 2007 and 2013 under FPGC's coverage.

MATERIALS AND METHODS

Section:

This was a retrospective cohort study that included all patients with breast cancer treated at INCan between January 2007 and December 2013 under FPGC's coverage. The study was canonical by INCan's Institutional Review Board. Individual patient files were reviewed to collect clinical, demographic, histopathologic, and follow-up data. The nerveless data was then validated and analyzed by a group of epidemiologists and oncologists.

Demographic and clinical data, such as historic period at diagnosis, menopausal status, torso mass alphabetize, reproductive hazard factors, and comorbidities, were nerveless. Clinical stage at diagnosis was determined using clinical and radiologic criteria. Patients were categorized into early on disease (stages I to IIA), locally advanced disease (stages IIB to IIIC), and metastatic disease (stage IV). Histopathology examinations were undertaken by specialized breast pathologists. Hormone receptor (HR) condition was determined using the Allred score by immunohistochemistry (IHC).^eleven An IHC calibration greater than two (1% to 10% of positive cells) was considered positive for both estrogen (ER) and progesterone receptors (PR). Cases with an Allred score of two or less were classified as ER or PR negative. Human epidermal growth factor receptor two (HER2) condition was adamant initially by IHC, followed past fluorescent in situ hybridization (FISH) in cases with 2+ membrane staining. Tumors were considered as HER2 positive in cases reported as iii+ by IHC or with an amplified FISH and negative in cases with 0+, 1+, and 2+ IHC staining with negative FISH amplification.¹² HR-negative, HER2-negative tumors were considered to be triple negative (TN).

All the patients were covered past the Seguro Popular public insurance scheme and had access to the same treatments and procedures. The choice of treatment was selected from the list of authorized interventions and medications included in Seguro Popular guidelines by each patient'southward treating oncologist. The covered interventions are shown in Table 1.

Table 1 – Interventions and Medications Included in the Seguro Popular Public Insurance Arrangement.xiii

The tumor response to neoadjuvant handling was besides recorded. A pathologic complete response (PCR) was defined equally the absence of rest invasive tumor both in the breast and in the axilla (ypT0/is, ypN0). Overall survival (OS) was calculated from the date of diagnosis to the appointment of last visit or death.

Descriptive statistics were used to clarify the clinical and demographic characteristics of the population. Measures of cardinal tendency and dispersion were used for quantitative variables, and frequencies were used for qualitative variables. OS was determined using the Kaplan-Meier method. Univariate and multivariate analysis using a Cox proportional hazards model were undertaken to determine which clinical and demographic characteristics were associated with worse Os. All statistical analyses were performed using STATA 5 12 (StataCorp 2011, Stata Statistical Software: Release 12; StataCorp, Higher Station, TX) A 2-sided P value < .05 was considered statistically significant.

RESULTS

Section:

Between 2007 and 2013, 5,500 patients with a diagnosis of chest cancer were treated at INCan, of whom 4,300 had complete clinical records and were included in this analysis. The demographic and clinical characteristics of the patients are shown in Table one. Mean age at diagnosis was 52 (±12.1) years, with 15.3% (northward = 645) younger than forty years of age. Forty-ane percent (n = 1,755) were overweight, and thirty% (northward = 1,284) were obese. Eleven per centum (n = 467) had diabetes, 18% (n = 7,530) had hypertension, and 5.two% (n = 223) had both. Regarding the presence of reproductive chance factors: 37% (n = 1,585) reported breastfeeding, boilerplate age at menarche was 12.8 ± 2.5 years, boilerplate age at kickoff pregnancy was nineteen.7 ± 4.5 years, age at menopause was 46.9 ± 5.half dozen years, and 22% (northward = 947) reported using contraceptive pills. Fifty-ane percentage of included patients (n = 2,203) were postmenopausal.

Clinical characteristics tin besides be found in Table ane. Most patients had locally advanced disease at the fourth dimension of diagnosis (53%, due north = 2,293), and 13% (north = 558) presented with stage IV illness. The most common histologic subtype was HR-positive, HER2-negative (lx.7%; n = ii,560), followed past HER2-positive (23.2%; n = 979) and TN (16%; n = 678). Neoadjuvant chemotherapy was administered to 1,834 patients (52%), with a PCR observed in 25.1% of patients (n = 460). Treatment modalities used are summarized in Table 2.

Tabular array 2 Demographic and Clinical Characteristics

Median follow-upwardly for the entire cohort was 40.5 months. Xx-four pct of patients (north = one,040) had recurrent or persistent disease, and 13% (northward = 551) died. V-year OS for the entire cohort was 82% (95% CI, 81% to 84%). The v-year OS for patients with early-stage illness was 97% (95% CI, 95% to 98%), whereas for those with locally advanced disease it was 82% (95% CI, eighty% to 84%), and for those with metastatic disease it was 36% (95% CI, xxx% to 42%). Survival curves co-ordinate to clinical demographic characteristics can be seen in Figure 1 . On univariate analysis, the following were shown to be associated with worse survival: age ≤ 40 years, avant-garde stage at diagnosis, lobular tumors, high histologic grade, and TN tumors. On multivariate analysis (stratified past histologic subtype), the stage at diagnosis, histologic grade, and immunophenotype remained significant after adjusting for handling variables (Table 3). Age was non a significant predictive factor for survival after multivariate analysis.

Fig 1 – Overall survival co-ordinate to relevant clinical and demographic characteristics. (A) Age; (B) clinical stage at diagnosis; (C) histologic grade; and (D) breast cancer subtypes. HER2, human epidermal growth cistron receptor ii; HR, hormone receptor.

Table three – Five-Twelvemonth Bone and Adventure Ratios for Death (multivariate analysis)

DISCUSSION

Department:

This work represents the first description to our cognition of a large cohort of patients with breast cancer treated in United mexican states under Seguro Pop'due south FPGC. Our data provide insight into the epidemiologic profile of Mexican patients with breast cancer, which is similar to that found beyond Latin America. Our patients had a relatively young age at diagnosis, showed a high prevalence of risk factors, and were diagnosed at advanced stages. In spite of that, most of the patients were alive 5 years from diagnosis, with an Os of 82%, which is comparable to that reported in more developed nations of the globe.^15,16

In Mexico, as in the rest of Latin America, the changing epidemiology of breast cancer is related to a high prevalence of risk factors, such as overweight, obesity, a depression rate of breastfeeding, low physical activeness, and high hormonal exposure.^7,viii,17-19 In add-on, the lack of loftier-quality health-related information represents a barrier to the implementation of successful prevention and early detection campaigns, which in turn leads to diagnosis at advanced stages and higher mortality rates.^7,twenty In this context, and because of the limited availability of personnel, equipment, and resource in the region, amend strategies to achieve main and secondary prevention and downstaging of the disease are desperately needed.²¹

The creation of the FPGC has provided access to wellness care to more than half of the previously uninsured population, as proven in this patient cohort, who otherwise would potentially not have received appropriate medical intendance. The patients included in this analysis were all treated according to the standardized multidisciplinary protocols stipulated by Seguro Popular's clinical guidelines, which allow for the employ of surgery, endocrine therapy, radiotherapy, and several cytotoxic chemotherapy regimens as well equally trastuzumab for patients with HER2-positive disease.¹³ For patients receiving neoadjuvant treatment using these guidelines, the PCR rate was 25%, which is similar to those previously reported in large pooled analyses of clinical trials.^22,23 This, along with the high 5-twelvemonth Bone in our serial, shows that access to treatment, and non ethnicity or socioeconomic condition, is the nearly important factor leading to good outcomes in breast cancer.

Our 5-yr OS of 82% compares favorably to that reported by the public sector in Mexico before the advent of Seguro Pop. For example, in a retrospective study from Mexico City'south Infirmary General, the reported 5-year Os for a cohort of 432 women with breast cancer treated between 1990 and 1999 was only 58.9%.²⁴ Of note, the stage distribution of this cohort was similar to ours, with ten% of women presenting with stage I, 52% with stage Two, 34% with phase 3, and merely iii% with stage IV disease. In those women who presented with stage Iii affliction, for case, the reported 5-year Bone was 45%, compared with 78% in our study, and this holds true for all stages. These striking improvements in outcome do not seem to exist dependent on the patients' characteristics but rather on admission to appropriate oncologic and supportive treatments.

I of the key findings in our study is the fact that near of the patients presented with locally avant-garde or metastatic tumors. In developed countries like the United states or the United Kingdom, < 20% of patients are diagnosed in such advanced stages, whereas in our population, 2 thirds of patients had advanced illness.^15,25 This cistron, which has been proven to have a negative impact on survival, is nevertheless modifiable through improvements in the health care system. Improving wellness-related education, strengthening early detection programs, creating mechanisms for prompt referral to specialized centers, and training health care personnel are of the utmost importance.²¹ Unfortunately, these aspects have not been improved by Seguro Pop, which is mainly designed to offer medical handling at specialized centers in metropolitan areas, thus having little impact on downstaging of the disease.¹⁹ The large number of patients with metastatic disease translates into college health care costs, particularly for patients receiving end-of-life intendance in the inpatient setting.²⁶ Furthermore, the low availability of palliative care resource in Mexico and in Latin America as a whole is a critical trouble faced by patients with advanced disease who may be receiving suboptimal care.² Thus, downstaging the disease would not only improve patient outcomes merely also lower spending for the entire health care system and allow for a ameliorate distribution of existing resources.

In that location are withal many shortcomings in Seguro Popular and in the FPCGC that should exist addressed and improved in the time to come. Besides the low investment in preventive measures, at that place is a lack of assigned resources for supportive care, and some medications that accept been proven to be effective for the handling of breast cancer are still non included. In addition, we besides found a high mastectomy charge per unit, which could be related to local practices or to patient-related barriers for the receipt of radiotherapy or adequate follow-up. Finally, at that place are nevertheless disparities on the bachelor resources to treat cancer between different regions of the country, with about specialized cancer centers located in large urban areas.

This study has limitations. These data come from a national cancer center located in Mexico City, and, as such, some interventions may not be available in other regions of the country where infrastructure is less adult and specialized health intendance personnel are defective. Even though INCan's patient population is representative of all social, cultural, and demographic backgrounds, just a small proportion of Mexicans receive their care at tertiary cancer centers similar INCan. Obtaining data from smaller cancer centers located in the various regions of the country would undoubtedly exist of peachy value to better understand the impact of Seguro Popular and, nosotros hope, to achieve national homogeneity in high-quality cancer intendance. Another limitation is the fact that our database lacks information on some specific characteristics of treatment, such as completion of planned chemotherapy, dose intensity, adherence to hormonal treatment, and chemotherapy toxicity. Nevertheless, the fact that fewer patients are lost to follow-up, coupled with higher survival rates compared with previous reports, may point that patients are in fact able to complete their planned treatments.

The creation of the FPCG has allowed our establishment, and other cancer centers in Mexico, to establish efficient and standardized mechanisms to care for patients with chest cancer, reducing the number of patients lost to follow-upwards to < 10%.¹⁰ Earlier FPCG was instituted, patients were treated erratically, their outcomes were worse, and their data was not collected and reported, which meant that there were no existent data regarding the landscape of chest cancer in Mexico. Seguro Popular has been benign for many Mexican women with breast cancer, and its databases stand for a unique opportunity to study breast cancer (and other malignancies) in Mexico. We believe that our feel in treating breast cancer under this scheme will allow the Mexican wellness care organisation, and other systems throughout Latin America, to evaluate their current practice and policies and to find new opportunities to improve the outcomes of patients with chest cancer in the region.

© 2017 by American Gild of Clinical Oncology

Conception and blueprint: Nancy Reynoso-Noverón, Cynthia Villarreal-Garza, Enrique Soto-Perez-de-Celis, Claudia Arce-Salinas, Abelardo Meneses-García, Fernando Lara-Medina, Enrique Bargalló-Rocha, Alejandro Mohar

Collection and associates of information: Juan Matus-Santos, María Teresa Ramírez-Ugalde, Alberto Alvarado-Miranda, Paula Cabrera-Galeana

Data analysis and estimation: Nancy Reynoso-Noverón, Alejandro Mohar

Manuscript writing: All authors

Final approval of manuscript: All authors

Accountable for all aspects of the work: All authors

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The post-obit represents disclosure data provided by authors of this manuscript. All relationships are considered compensated. Relationships are self-held unless noted. I = Immediate Family Member, Inst = My Institution. Relationships may not relate to the subject matter of this manuscript. For more than data about ASCO's conflict of involvement policy, please refer to world wide web.asco.org/rwc or ascopubs.org/jco/site/ifc.

Nancy Reynoso-Noverón

No human relationship to disembalm

Cynthia Villarreal-Garza

Consulting or Advisory Role: Myriad Genetics, Roche

Travel, Accommodations, Expenses: Roche, Myriad Genetics

Enrique Soto-Perez-de-Celis

Travel, Accommodations, Expenses: Amgen, Bristol-Myers Squibb

Claudia Arce-Salinas

No relationship to disclose

Juan Matus-Santos

No relationship to disclose

María Teresa Ramírez-Ugalde

No relationship to disembalm

Alberto Alvarado-Miranda

No relationship to disclose

Paula Cabrera-Galeana

Consulting or Advisory Role: Pfizer

Abelardo Meneses-García

No relationship to disclose

Fernando Lara-Medina

No relationship to disclose

Enrique Bargalló-Rocha

Speakers' Bureau: Genomic Health

Alejandro Mohar

No relationship to disembalm

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Section:

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Source: https://ascopubs.org/doi/10.1200/JGO.2016.007377

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