In order for cells removed during a biopsy to be examined, they must be put on a slide, stained, and then looked at under a microscope. Cells are judged based on a number of criteria, including the size and color of the nucleus (the center of the cell that contains DNA), the appearance of the other structures in the cytoplasm (the area between the nucleus and the outer wall of the cell), and the overall size of the cell itself.

A biopsy examines cells under a microscope

For centuries, pathologists (physicians who identify diseases by studying cells and tissues under a microscope) have been trying to predict how cells will behave based on how they appear. We know that cancer occurs when a cell becomes damaged. But this damage does not occur in one step. Instead, it takes a series of “mistakes” for a cell to be transformed from a normal cell into a cancer cell, which has the ability to grow uncontrollably and to live outside the organ where it started.

Because our bodies make hundreds of millions of new cells every second, there are billions of opportunities each day for mistakes to occur in the genetic code inside a cell’s DNA. Most of the time our bodies are able to find and repair or destroy these mistakes, but not always. Some mistakes slip by. And when the cells that carry a genetic mistake reproduce, they are prone to make more genetic mistakes. These mistakes in the genetic code inside the DNA can be reflected in the appearance of the cell, making it look abnormal.

It takes a series of genetic “mistakes” for a cell to be transformed from a normal cell into a cancer cell

What the precise problem is, though, is impossible to say. Sometimes cells that look bizarre behave in a bizarre fashion. But other times cells that look very bizarre still behave fairly normally. It all depends on which genes are damaged when the cell reproduces and the microenvironment the cells live in. Further, when looking at a cell on a slide a pathologist has no way of knowing if that cell was about to be repaired or if it was going to go undetected. The pathologist also can’t determine how many mistakes have occurred within the genes and thus how close the cell might be to becoming cancerous. All the pathologist can say for sure is that the cell looks abnormal and that some damage has taken place.

The problem with the current method pathologists use to examine cells is that it is very subjective. The pathologist must determine how far from normal a cell looks, yet there is a wide variation in what is considered to be normal. This is why the experience of the pathologist reading the slides is important and why it can be helpful to get a second opinion from another pathologist. It is hoped that in the near future pathologists will be able to analyze the genetic composition of the nucleus directly to determine how damaged a cell is. This will provide better information than that obtained by judging a cell’s damage by how it looks.

As pathologists have learned more about cells and how they change, it has become clear that what matters most is how far from normal a cell looks because the less normal the cell is in appearance, the greater the chance that genetic damage has occurred. And when genetic damage has occurred, a cell has the potential to become cancerous. This does not mean that a damaged cell will turn into a cancerous cell; it means it might. This drawing illustrates the potential progression from hyperplasia and/or atypia to invasive cancer.

Hyperplasia is the first type of abnormality in a cell’s appearance. It means that there are more cells than you would expect to see in the walls of the ducts or lobules, but that all of these cells appear normal. A diagnosis of hyperplasia does not put you at any increased risk for developing breast cancer.

Atypia means that the cells look different from normal cells. You can have atypia with hyperplasia, which means that the cells look different from normal and that there are more cells than you would expect to see. You can also have atypia without having hyperplasia. A diagnosis of atypia does not mean you have cancer or even pre-cancer. It means you might have a pre-pre-cancer. In fact, most women with atypia never get breast cancer. Rather, a diagnosis of atypia means that you have a “marker” of being at increased risk for developing cancer. The increased risk for a group of women with atypia is one percent higher than it is for a group of women who do not have atypia. If a woman does not develop breast cancer in 10 years after being diagnosed with atypia, then her risk drops off significantly. In fact, it is not uncommon for a repeat biopsy in the same area of the breast to show entirely normal-appearing cells.

The terms ductal and lobular indicate where the cells originated. Ductal means that the unusual cells are in the ducts, the passages that the milk travels through to get to the nipple. Lobular means that the unusual cells are in the lobules, the parts of the breast capable of making milk. Atypia and hyperplasia are thought to be reversible, although it isn’t clear what can nudge them back to normal. Atypical ductal hyperplasia (ADH) increases your risk of breast cancer occurring in the breast where the ADH was found. Atypical lobular hyperplasia (ALH) increases your risk of developing breast cancer in both breasts. Keep in mind, though, the vast majority of women diagnosed with ADH or ALH never go on to develop breast cancer.