Cancer

Cancer

Cancer is the name of a collection of related diseases. Specifically, all cancers undergo an uncontrolled proliferation of the patient cells, which spread into surrounding tissues. In a normal organism, cells grow and divide to maintain the tissue. As cells grow old, or accumulate too much damage, they undergo cell death and new cells will take their place. However, in cancer, this orderly process breaks down. Cells refuse to die when they get old, or accumulate damage. New cells are formed even if they are not needed. In consequence they form purpose-less growths called tumors.

This abnormal behavior occurs as consequence of the alteration of crucial genes. These alterations can be inherited from our parents, or acquired during our lifetime due to replication errors or exposure to DNA-damaging substances. As with any other phenotypic trait, the likelihood of developing cancer will be determined by the interplay between our genetic background and the environment: genetic backgrounds may favor or hinder the acquisition of mutations, and so do environmental factors.

Breast cancer

Breast cancer occurs when breast cells undergo this uncontrolled proliferation. In most of the cases they begin in the ducts that carry the milk to the nipple. However the tumor can originate in other tissues, mainly the milk-producing gland.

Breast cancer is the second most commonly diagnosed cancer among women, after non-melanoma skin cancer. We find the highest incidence in Western countries, and it has increased in the last decades. Two proposed explanations are more diagnoses due to mammography screening, or more cases due to the generalization of hormone treatments for menopause. It is also the second leading cause of cancer deaths after lung cancer. Encouragingly, the prognosis is better every year (5y survival rate > 80% in France) thanks to improvements in treatments and better screening. Unsurprisingly, the mortality is higher in developing countries. It is mostly a women’s disease: only about 1% of the diagnosed cases are in men. Among the most important risk factors for breast cancer we can highlight age, family history, reproductive history, usage of oral contraceptives, overweight, physical activity and exposure to radiation.

Breast cancer subtypes

Breast cancer is a very heterogeneous disease: while all the tumors appear in the same organ, the tissue where they originate, the molecular mechanism involved, the response to therapy, etc. vastly differ. In general, clinical decisions are based on the expression of 3 molecular markers: the expression of the endocrine receptors for estrogen and progesterone (ER and PgR, respectively) and the overexpression of the HER2 gene. The proteins these three genes code for are targets for chemotherapy. Based on the results, we distinguish three main breast cancer subtypes: hormone receptor positive, HER2 positive and triple negative.

Hormone receptor positive

Hormone receptor positive tumors include the tumors expressing ER and/or PR, which respectively depend on estrogen and/or progesterone to grow. They happen mostly in postmenopausal women. HR+/HER2- also known as LuminalA are the majority of breast cancers (60-75%) and they present the best prognosis.

HER2 positive

HER2+ tumors depend on the protein HER2/neu (human epidermal growth factor receptor 2) to proliferate, which they over-express. HR+/HER2+ (also known as LuminalB) constitutes 10% of the cases, while HR-/HER2 (also known as HER2-enriched) involves 5% of them. There are a couple of very effective drugs against it.

Triple-negative

Triple-negative tumors (also known as basal-like) lack the expression of all three of ER, PgR and HER2. These patients present a worse prognosis than the rest, due to the aggressiveness of the tumor and the lack of a clear molecular target. Still, the main treatment is chemotherapy.

Screening

Routine screening for breast cancer has been set up in the last decades in many countries. After it was introduced we observed a mortality reduction of 30%, justifying its wide implementation. It consists on yearly mammographies. This technique uses low resolution X-rays to detect lesions in the breast. If the lesion is big enough, further morphological examination allows to characterize if the lesion is benign or malign. However, most of the screen-detected lesions are small. In consequence, we perform an additional intervention (biopsy or advanced imaging technique) to make the diagnosis.

Despite the aforementioned success, there is a big controversy regarding mammography programs usefulness. That is because, in practical terms, the 30% decrease in mortality means that for every 1000 women examined, we will save 7-9 lives. On the other hand, it will provoke with 4 cases of overdiagnosis, tumors that would have never progressed to symptomatic presentation during the lifetime of the woman. That, and many more cases which will require further, possibly invasive, testing to make the final (negative) diagnosis. The proposed solution to this involves adapting the screening process to different demographic groups, so that high risk groups are closely watched while low risk groups loosely so.

References

  • PDQ® Cancer Genetics Editorial Board. PDQ Genetics of Breast and Gynecologic Cancers. Bethesda, MD: National Cancer Institute. Updated 30/03/2017. Available at: https://www.cancer.gov/types/breast/hp/breast-ovarian-genetics-pdq. Accessed 14/04/2017. [PMID: 26389210]