Increase is more pronounced among women under 40 years old
Sandra Jávera
Mococa is a quaint little town in upstate São Paulo where life moves at a slow pace. Some 260 kilometers (km) from the state capital, the municipality, population 67,000, became a pioneer in an important public health program at the end of April after a computerized system that revolutionizes the way breast and cervical tumors are tracked in Brazil was put into operation at two of the town’s thirteen public health centers (UBS).
Instead of waiting for women to seek an appointment within the public health system, only then being referred on by general clinicians for preventive gynecological tests, staff at these UBS will actively seek out these women. Aided by a computer program that cross-references Brazilian Ministry of Health data with those of the municipality, they will be identifying local residents in the highest risk age group for these two cancers, and when the time is right, inviting them to undergo a mammography—a specialized scan to identify alterations and nodules in the breasts—and a Pap smear, named for Greek physician George Nicholas Papanicolaou (1883–1962), who developed this test to identify incipient lesions in the cervix. Healthcare teams will also provide aftercare to women needing diagnosis confirmation tests and treatment.
The idea behind changing this procedure is to capture any treatable tumors and reduce the time frame between identification of the cancer and commencement of the treatment. It is hoped that in this way a trend in São Paulo and across the rest of Brazil in recent years will start to be reversed: increased mortality rates from breast and cervical cancer, particularly among younger women below the age of 40.
“The pilot implementation at two Mococa health centers is a real-world test of organized tracking. It will help us to identify any issues arising and perform all the necessary adjustments and refinements before rolling the system out across the other municipal centers,” explains public health physician Victor Wünsch Filho, of the School of Public Health at the University of São Paulo (FSP-USP), and CEO of the São Paulo Oncocentro Foundation (FOSP), which coordinates breast and cervical cancer tracking programs across the state.
Some years ago Wünsch and his team at FOSP began to perceive that the system for early detection of breast and cervical tumors adopted in São Paulo and other states, based on an opportunistic approach, was not producing the desired effect—and they decided to act. Supported by researchers from three São Paulo universities and the World Health Organization’s International Agency for Research on Cancer (IARC-WHO), the group formulated a program to shift the passive tracking strategy to active—ConeCta-SP, funded by FAPESP and the State Health Department—and started to put it into practice in 2022.
Since then, the FOSP specialists have interviewed 437 women and 400 healthcare professionals from 50 UBS across the state to identify the barriers to performing the tracking tests. They also initiated workshops with managers of the 17 regional and municipal healthcare departments to help them reorganize the system and implement the changes. The most recent advance came on April 24 in Mococa with the experimental IT platform, which assists in identifying women who should be undergoing preventive gynecological exams, going online. The platform is expected to go live at the UBS across another 19 municipalities in the region by the end of June, and then at other regional health departments in São Paulo before September.
Transforming the way women access preventive exams, and monitoring them more closely after diagnosis, is an attempt to flatten the mortality curve for these cancers in Brazil, which could—and should—be different. In São Paulo, after a relevant period of reduction, whose extension varies according to the type of cancer, the death rate from breast and cervix tumors has begun to trend upwards again. About three years ago, researchers from FOSP identified an inflection in mortality curves in the state from 2015 (see Pesquisa FAPESP issue n° 320), and, more recently, evidence began to accumulate that the same phenomenon appears to be occurring across Brazil, and could have started even earlier.
In an article published in the journal BMC Cancer in January, oncologists Jessé Lopes da Silva and Andreia de Melo, and epidemiologist Luiz Claudio Thuler, all of the Brazilian National Cancer Institute (INCA) in Rio de Janeiro, evaluated the evolution of the death rate by breast cancer in the country from 2000 to 2021. Breast cancer is the second most common neoplasia in women in Brazil (behind only nonmelanoma skin cancer), and the biggest killer. This year, 73,600 new cases of breast neoplasias and 18,000 deaths are expected.
Data from the Mortality Information System (SIM) of the Brazilian Public Health System’s Healthcare IT Department (DataSUS) obtained by researchers indicate that in the 22 years analyzed, deaths resulting directly from breast tumors rose in a practically continual manner in the country. In 2000, there were 10.5 deaths for every 100,000 women, while the figure in 2021 was 11.8 (see graph), an upawrd trend despite the rate of incidence (number of new cases per year) having remained stable. In real terms, this incidence fell slightly for the overall population, with a statistically insignificant reduction, and grew among women under 40.
Alexandre Affonso / Pesquisa FAPESP
“If the overall incidence did not change, it was expected that mortality would remain constant or decline, since Brazil has a tracking program for early identification of breast tumors at a stage when the treatment is more successful,” says Thuler. Law n° 11.664, of 2008, assured free breast scans for all women over 40 on the SUS. A 2015 ordinance issued by the Brazilian Ministry of Health restricted the test to the 50–69 age group, which was maintained by Law n° 14.335, of 2022. Although the incidence is increasing in developed countries, the mortality rate has been falling because their tracking works well and gets women into treatment in the initial stages, with a higher cure rate,” says the epidemiologist. “In Brazil we are going against the desired trend.”
In the BMC Cancer study, Silva, Thuler, and De Melo also noted that the increased mortality rate was higher among younger women, growing an average 1.8% per year for those under 40, while this rate was three times lower (0.6% per year) in the 50–69 age range and halved (0.9% per year) among those over 70. A similar effect was observed by epidemiologist Miranda Benoudia, of Canada’s University of Calgary, and her team. In an article in Nature Medicine, the group compared evolution of the breast cancer death rate in 46 countries, and found that Brazil was one of the seven in which the rate increased between 2008 and 2015, more markedly so among women under 50.
There is also an ethnic disparity associated to breast cancer in Brazil. In another analysis, Silva, Thuler, and colleagues compared the progression of the death rate between White and Black people from 2000 to 2020, and found that it grew almost four times faster in the latter group than in the former. The average mortality rate increased at 0.6% per year among White groups, and 2.3% for Black groups, although breast tumors were more frequent in White women (there were 101 cases for every 100,000) than in Black women (60 in 100,000), according to results published in 2024 in Breast Cancer Research and Treatment. “Generally speaking, Black women have a lower level of education, live in poorer regions, and come up against more barriers to diagnosis and treatment access,” says Silva.
“Identifying and treating breast cancer in young women is a challenge,” says oncologist Maria Del Pilar Estevez Diz, of the USP School of Medicine (FM-USP) and director of the clinical body at the São Paulo State Institute of Cancer (ICESP), Brazil’s biggest oncology hospital. According to the specialist, who did not participate in the mortality studies, the reasons are many. One is that women under 50 do not fall within the target group of public-sector healthcare tracking programs, which cover around 75% of the Brazilian population, restricting access to preventive scans. Women in this group also have denser breasts, with more milk-producing tissue and less fat, which hampers the identification of any alterations during the mammography. More aggressive cancers, which spread more quickly, are also more frequent in this age group. “Physicians need to pay attention and value the complaints of these patients, considering the possibility of cancer,” she says.
Whether in the breast or other areas of the body, cancer is a more frequently occurring illness with advanced age. Over the years, the cells lose the capacity to correct any anomalies arising in the genetic material during cell division or as a consequence of exposure to carcinogenic environments such as sunlight, alcoholic beverages, smoking, or pollutants. These anomalies consequently multiply unchecked, giving rise to cancer.
“In 80% to 90% of cases, cancer emerges spontaneously due to a buildup of defects in the DNA over the lifetime,” explains specialist genetics oncologist Maria Aparecida Koike Folgueira, also a professor at FM-USP and ICESP researcher. “The remainder is of hereditary origin. The person inherits altered genes from their parents that favor the development of cancer.” This seems to be the case for a relevant proportion of breast tumors occurring in younger women.
Sandra Jávera
In a study coordinated by Folgueira, oncologist Rodrigo Santa Cruz Guindalini analyzed the genetic profile of breast tumors in 1,663 women from all regions of Brazil. Of the total, 335 (20%) presented tumors arising from hereditary genetic alterations, according to an article published in 2022 in the journal Scientific Reports. Among women under 35 this proportion, as expected, was considerably larger from a statistical point of view: 25.8%. More frequently altered genes were BRCA1, BRCA2, and TP53, which repair random errors arising in the DNA.
A change in the mortality pattern similar to that observed for breast neoplasias has also been recorded over recent years in Brazil for cervical cancer. This is the fourth most common type of cancer (including nonmelanoma skin tumors), and the fourth most lethal. The estimate is that in 2025 there will be 17,000 new cases and 7,000 deaths in the country.
The first signs of inversion in the mortality trend were noticed by the FOSP team and documented in an article published in 2023 in Revista de Saúde Pública (Public health journal). In the study, epidemiologist Carolina Luizaga analyzed the evolution of cervical cancer mortality in Brazil between 1980 and 2020. Over these four decades, the proportion of women dying from this type of neoplasia in each group of 100,000 has fallen by almost half: 10.1 in 1980 and 5.6 in 2020.
This overall trend, however, masks important contrasts. When she looked at shorter periods, Luizaga found that at national level, the mortality rate stopped falling in 2014 and thereafter became stable, as published in Revista de Saúde Pública. São Paulo State, however, went against the national pattern, with cervical cancer deaths growing from that year at a rate of 1.2% per annum.
The effect observed in São Paulo was more intense and applicable to all of Brazil when the FOSP team analyzed the trends by age group. The drop in the mortality rate ceased among younger women between 25 and 39, with the rate growing from 2007 at 2.5% per year. This effect began a little earlier in Brazil’s Southeast—2006—and increased (5% per year) from 2013. “The data clearly indicate that this trend inversion occurs due to an increased death rate among young women,” says Luizaga. The FOSP group suspects that similar behavior will be seen for breast cancer, but the data collected are still being analyzed.
What Luizaga and colleagues began to perceive years ago for cervical cancer has now, to a certain extent, been confirmed by the team of Tainá Raiol, from the University of Brasília (UnB) and the Oswaldo Cruz Foundation (FIOCRUZ) in the federal capital. Investigating national data for the period 2000–2021, Matheus Santos Melo, a doctoral student of Raiol, found that from 2014 onwards, the mortality rate from cervical neoplasias stopped falling and demonstrated a slight increase. Once again, this growth is largely attributed to younger women. Mortality increased for women between 20 and 29 over the entire period analyzed, and from 2011 for those in the 30–39 and 40–49 age ranges, according to an article published in October in Scientific Reports (see graph below).
Alexandre Affonso / Pesquisa FAPESP
“These data indicate that Brazil is far from achieving the goal, proposed in 2020 by the WHO, of eliminating cervical cancer deaths as a public health issue. To achieve this you would need to reduce the number of new cases per year—the rate of occurrence—to 4 in every 100,000 women. The rate today is 15.4 per 100,000, with the mortality at 5.8 per 100,000 in Brazil,” concludes Melo.
While breast cancer occurs more frequently in richer regions and countries, associated as it is to obesity, smoking, alcohol consumption, and sedentary lifestyles, malign cervical cancer tumors are more common in poorer areas. The good news is that cervical neoplasias can easily be prevented by vaccination. In around 98% of cases, malign tumors of the cervix arise from infection by the human papilloma virus (HPV), against which the Brazilian public system has provided immunization since 2014. “The vaccine prevents 90% of cases of this cancer,” says surgeon Reitan Ribeiro, of McGill University in Canada, and vice president of the Brazilian Society for Oncology Surgery (SBCO). “If I was a public administrator, I would back immunization to eliminate the problem,” he states.
The vaccine generates immunity against four types of the virus (two associated to cancer, and two to genital warts), and is recommended for girls and boys between 9 and 14 years of age, when the vast majority has not yet commenced any sexual activity. At populational level, however, its protective effect becomes evident years later, since cervical tumors and other cancers associated to HPV evolve slowly. In its strategy to eliminate cervical cancer, the WHO proposes that 90% of girls be vaccinated before they reach the age of 15. In Brazil, however, coverage has fallen short of this in recent years. Data from the Ministry of Health indicate that the vaccine reached the entire target group in the early years, but began to decrease from 2017. Last year, 82.5% of girls between 9 and 14 were vaccinated (see graph).
Alexandre Affonso / Pesquisa FAPESP
At least for now, though, this decline in immunization does not explain the recent increase in mortality. The most plausible rationale, valid for both breast and cervical cancer, is the lack of an efficient tracking system and timely treatment. Law n° 12.732, of 2012, stipulates that a SUS cancer patient must receive their first treatment within 60 days of the diagnosis being confirmed. In the case of malign breast and cervical tumors, however, this target is not often achieved, despite a recent improvement.
According to data from the DataSUS Oncology Panel, in 2024, treatment of 41% of breast cancer cases commenced after the time limit defined by the law. In the case of cervical neoplasias, the proportion beginning treatment late was even higher: 47.7%. Two studies in which epidemiologist Marianna Cancela of INCA participated indicated a significant regional disparity. For breast tumors, the delay varied from 33% in the state of Rio Grande do Sul to 57% in the state of Acre, according to an article published in 2021 in Scientific Reports. According to data published in 2023 in the journal Ciência & Saúde Coletiva (Collective science and health), the proportion of cervical neoplasias was 38% in Piauí and 65% in Rio Grande do Norte.
One consequence of these delays is that when the patient comes to see the doctor, the tumor is often in an advanced state of progression, requiring more modern therapies not always available on the SUS, making the treatment less effective and reducing the chance of cure. “There is a glaring difference between treatment options for advanced tumors available on the SUS and in the private system,” says surgeon Fabiana Makdissi, leader of the Breast Tumor Reference Center of the A.C.Camargo Cancer Center, in São Paulo.
In addition to flaws in tracking and in the offer of treatment by the public health system, personal reasons appear to contribute to delayed identification and treatment of these female cancers. In São Paulo, the 437 women interviewed before implementation of ConeCta-SP listed a series of reasons for not undergoing preventive exams within the appropriate time frame. Many were afraid of finding something wrong, or were embarrassed to do the tests, while others claimed not to have the time, or to find the procedure unnecessary, since they were “not feeling anything untoward.” They also reported facing barriers in the public system, such as difficulties in scheduling the exams, and long wait times.
In São Paulo, things are expected to change, and mortality rates to come back down, with the advance in the new tracking strategy, accompanied by awareness-raising campaigns for women and adjustments in the offer of treatments. The challenge is to do this as quickly and as effectively as possible for a group of almost 15,000 people. At the end of 2022, Pernambuco State embarked upon a similar program—the Uterus is Life—with the health system under reorganization to actively monitor cervical cancer. The expectation is to monitor 370,000 Pernambucan women during the pilot phase, still being implemented. “Opportunist tracking worked up to a point. Then it lost its effectiveness and impact on mortality,” states Luizaga. “It’s time to change.”
The story above was published with the title “Avoidable losses” in issue 351 of May/2025.
Project Cancer management in the state of São Paulo (ConeCta-SP): From knowledge to action (n° 21/11794-4); Grant Mechanism Science Centers for Development; Principal Investigator Victor Wünsch Filho (FOSP); Investment R$2,710,904.14.
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