Hormones dominate breast cancers in men

2023-10-18 11:18:06

On the occasion of World Breast Cancer Day, October 19, the oncologist and GEICAM researcher, Noelia Martínez Jáñezin an interview with EFEsalud, details some of the data provided by the first and only registry of breast cancer in men in Spain with data from 772 patients from 54 hospital centers.

“We are currently reviewing all the data obtained in this retrospective study” with the aim of proceeding to its scientific publication in the coming months, says the doctor who coordinates this registry together with the oncologist Ander Urruticoechea.

This is information from clinical practice from 2000 to 2019, a period in which there has been a revolution in diagnosis and in the most personalized and innovative treatments based on the subtypes of breast cancer and its genetic alterations. .

And it sheds light on breast cancers in men since it is considered a rare disease, affecting approximately 1% of all annual diagnoses of this tumor, about 35,000 in Spain, so about 350 are in men.

Different incidence in the subtypes in men and women

One of the main conclusions refers to the classification into the big three breast cancer subtypes.

In this series of 772 male patients, 98% had had a tumor of tipo luminal (hormonal), and the rest are cases of HER2 y triple negative.

“They are the same subtypes but not the same incidence as in women, there is a big difference,” highlights Noelia Martínez Jáñez, since, although the luminal is also the majority in them, the percentage is 70-75%, while HER2 accounts for 25-30% and triple negative occurs between 5 and 10% of cases.

Furthermore, the doctor specifies, in data series carried out in other countries, luminal (hormonal) types in men are also the majority, 90%, but in none has it been as high as 98% in the Spanish registry.

A balance between estrogen and androgen

A hormonal imbalance, with a greater presence of estrogen (the predominant hormone in women) than androgen (the predominant hormone in men), could be one of the risk factors for male breast cancer.

An example is Klinefelter syndrome, a rare genetic disorder that occurs when a male has an extra copy of the X chromosome (XXY), which favors higher levels of estrogen and lower levels of androgen.

The doctor explains that there are also liver diseases, for example cirrhosis, that affects this hormonal balance, even overweight and obesity in men can influence, although all these factors described in the literature are not reflected in practice. usual clinic, most patients do not have them. “In our series, we don’t have that information,” she points out.

Conventional treatments (surgery, chemotherapy and radiotherapy) and innovative treatments (monoclonal antibodies directed at molecular targets and immunotherapy) are the same as in women.

Even hormonal treatment, which stops estrogen in the luminal subtype and which women must take for at least five years, is also a therapy prescribed to men, although to a greater extent with tamoxifen than with aromatase inhibitors (these latter intended for postmenopausal women).

From left to right: Oncologist Noelia Martínez; Marius Soler, patient and president of the INVI Association and the urologist Ignacio Moncada. Photo provided

Family background and genetic alterations

The researcher explains that in this registry it has also been seen that, “in a slightly higher percentage” than in women, men present the genetic alterations associated with breast tumors such as BRCA1 and BRCA2, CHECK2 or ATM, so It is always mandatory to send them to genetic counseling.

Given that the study has clinical data since 2000, “previously not all patients had been referred to genetic counseling services, something that is now mandatory,” says the also oncologist at the Ramón y Cajal University Hospital in Madrid.

Male patients also have family background with breast cancer and have suffered in some cases a second tumor. The age of diagnosis It is somewhat later than in women: in women it is from 55 years of age and in men from 60.

Another reading of this registry is that in the series of 772 patients “there are few cases with metastatic disease” in relation to other studies, but they are “still immature data” and that draw the attention of researchers since in other series there is a higher percentage of locally advanced and metastatic tumors.

Hence, one of the main challenges is early diagnosis, now limited by the lack of knowledge and awareness that men can also be targets of breast cancer, even if they are a minority.

“When they notice a lump in the breast area, they should go to the Primary Care doctor to be referred to the breast units of the hospitals,” the doctor warns.

Establishing screening programs, such as mammography for women, for such a low percentage of affected men is something that is not contemplated, in addition to this diagnostic test not being useful because the size of the man’s breast is not sufficient and in many cases Other diagnostic techniques must be used, such as ultrasound or magnetic resonance imaging.

The ARDERNE project, paving the way

Also, this low number of cases of breast cancer in men does not encourage the design of clinical trials aimed only at them.

GEICAM is currently developing the ARDERNE research project, a continuation of the patient registry, to deepen the knowledge and approach to this cancer in men.

“The main objective is a genetic and molecular characterization of tumor and blood samples from patients that leads to a relevant clinical classification, so that a predictive tool can be generated to know and use in men with breast cancer in the usual practice,” says Noelia Martínez Jáñez.

“The first thing,” he adds, “is to describe what we have in Spain, which is not defined, and we may find surprises…Perhaps our patients are diagnosed earlier and there are fewer locally advanced and metastatic tumors than others published in other series.”

The researcher points out that the ideal would be to compare it with a group of cases in women, but there is no retrospective female record in Spain from 2000 to 2019. “It is very complex,” she laments.

A project, ARDERNE, “ambitious” and with several lines of research that are moving forward depending on the financial resources collected.

“We are underway with several genetic, genomic, molecular and proteomic analyses, thanks to the economic effort made by the GEICAM group itself, such as obtaining financing through international projects and scholarships, to which we apply, without forgetting donations. of patients, companies and the INVI Male Breast Cancer Association that allocates the proceeds for this study,” he indicates.

“Despite all this, we are far from being able to determine everything proposed, but we do not stop seeking funding to move forward,” concludes oncologist Noelia Martínez Jáñez.

Hand in hand with patients

Who they do count on for research is the patients of the INVI Association with which GEICAM It has been collaborating since 2020 to provide a more complete view of this tumor in men.

Marius Soler49 years old, is the president and founder of this organization that is committed to research and seeks to raise awareness among men that they can also be victims of breast cancer, leaving aside prejudices and misinformation.

Six years ago she was diagnosed with an already metastatic tumor since she had not given importance to that lump next to her nipple, believing it to be a fat cyst.

He had to go to his wife’s gynecologist. He didn’t know which specialist to go to. After a difficult path, with bone metastases, he was treated with cyclin inhibitors that were not prescribed for men.

“Soon I was in complete remission. It was an impact on my life and for research. I have been in treatment for six years with a semi-acceptable quality of life,” says the president of INVI, who emphasizes the need for early diagnosis and expanding knowledge of a tumor that also it’s a man thing.