By Dr. Kathleen T. Ruddy
As promised, here is the next installment in my fall lecture series about the human breast cancer virus: Cancer, The Immortal Renegade: Or, Why You Can’t Catch A Monkey By Chasing It
One morning, two women—each thirty-five years old, living in the same town—wake up, take a shower, and find a lump in their breast. Neither of them has had any breast problems in the past, nor is there a history of breast cancer in their families. Let’s assume for the sake of argument that both lumps are painless and about the size of a dime. Both of these women go to their doctors within a week and have a mammogram and breast ultrasound. The radiologist says the lumps are clearly visible and are solid. Biopsies are then performed to answer the question, What is causing the lump? These two women also happen to go to the same hospital for their breast biopsies, and the same pathologist examines their biopsy tissue. One woman is told she has a benign tumor. Of course, she is so relieved she can breathe again. Unfortunately, the other woman is given the worst news anyone who’s had a breast biopsy can hear: she has cancer. She doesn’t think she’ll ever be able to take a deep, relaxing breath again.
Exactly what did the pathologist see under the microscope? Precisely what distinguishes a benign tumor from the one that is malignant? Both lumps looked the same on mammogram and ultrasound. Both were solid and the same size. From all outward appearances, these two lumps looked identical. So what was seen down the microscope that rendered one a cancer and the other benign? , what we are asking is What are the visual and biological characteristics that differentiate benign tumors from those that are diagnosed as cancer? Understanding the differences between benign and malignant tumors is at the heart of understanding the incredible challenges that face anyone who hopes to cure, or be cured, of cancer.
Let’s start with some common misconceptions about tumors in general, and then we can move on to a more detailed discussion of cancer, per se. Many people believe that cancers grow fast and benign tumors grow slowly. But that’s not always true. Some breast cancers grow very slowly. I once had an elderly patient whose doctor had been following a mass seen on her mammogram for five years. The mass, which was not deemed suspicious by the radiologist when it was first seen, and which was not palpable on physical examination (i.e., neither the patient or her doctor could actually feel it) had not changed whatsoever over the course of five years. Every year, this woman faithfully had her annual mammogram, and every year the mass was there, seemingly immutable as the Rock of Gibraltar, and she and her doctor were told there was nothing to worry about. Then one day the patient felt a lump in her breast. The lump happened to be in the same breast that also harbored the “entirely benign” mass seen on her mammogram for the previous five years. In fact, the lump that she could now feel in her breast corresponded to the mass on the mammogram but it had When her physician referred her to me, the lump felt like cancer. A repeat mammogram showed a mass just where the old one had been – the one that had been watched for five years – only now the lump was very large and had extended to her axilla (the tissue under her arm.) I did a biopsy and discovered that she had had cancer all along. Her tumor, however, appeared suddenly five years before, stopped growing, went into a state of dormancy, and then began growing vigorously. So grow, whether rapid, slow, or intermittent, is not a reliable way to distinguish a benign from malignant tumors. Indeed, some benign tumors can grow, scaring the daylights out of patients and their primary care physicians. While rapid growth is often a hallmark of cancer, this is not always the case. In summary, the difference between benign and malignant cannot be differentiated by virtue of the rate of their growth.
What about pain? Most women believe painful lumps benign, and are often relieved to find that a new lump in their breast is painful. They think, “Oh, good, this isn’t cancer.” But 15% of breast cancers are painful; o pain is not an accurate either.
They answer lies at the bottom of the microscope, which is why all breast lumps need a biopsy (or something as reliable) to rule out the presence of a cancer. under the microscope cancer cells look distinctly difference from normal cells. It’s as if you see someone with only one eye, not two; or someone with two noses, not one; or someone with three heads. You’d know right away there was something wrong, for ‘normal’ human beings have one head, two eyes, and one nose. When a pathologist looks down the microscope at a biopsy specimen, identifying cancer cells is usually not much of a challenge. (Of course, there are occasions when the cells seen on a biopsy specimen are abnormal but not frankly cancer, at least not yet. They may or may not be on their way to becoming cancer. But this situation represents only a minority of cases, and so I keep to my generalization above that cancer cells are pretty easy to spot on a biopsy specimen compared to “benign” tumor cells.)
O.K., so cancer cells look really different – actually, they look bad. And that’s because they are. As to behavior, which is the most important consideration, how does the biologic behavior of malignant tumors differ from that of benign tumors? Generally, hree characteristics that they way behave from that of normal cells: Cancer cells have the unique ability to invade, metastasize, and live forever. Let me explain these three characteristics separately so you can fully appreciate what we (patients and doctors) are up against when the pathologist looks down the microscope and then looks up and says “This is cancer.”
First, cancer cells invade. By this I mean that they do not respect the natural borders set up by other cells and tissues in the body. As an example, a benign tumor in the lung may grow quite large, pushing and pressing on the surrounding tissue structures like the ribs and heart. But a benign tumor, even if large and fast growing, will not “eat” into the surrounding tissues. A benign tumor will surely press up against them, but the tumor and the surrounding structures will be squished together like too many children crammed into the back seat of a car: shoulder to shoulder and none too happy about it. On the other hand, a malignancy like lung cancer will grow right into the surrounding tissue. Not satisfied to merely press up against the surrounding structures, a malignant lung tumor will ‘eat’ into the esophagus, the windpipe, and even the heart – literally strangling the patient to death from the inside out. This is what’s known as invasion. Cancer cells invade. Benign tumor cells just crowd and press up against other cells and structures. As for breast cancer, it can invade the overlying skin of the breast; it can invade the muscle behind the breast; and I’ve even seen it invade a blood vessel behind the rib of the breast, causing the unfortunate patient to bleed to death.
When the pathologist looks at the biopsy tissue under the microscope cells invading surrounding tissue that these cells are cancerous and not benign.
Second, cancer cells metastasize. That is, they travel; they ‘hit the road’. Individual cancer cells can break free of the tumor, say in the breast, and enter the bloodstream and lymphatic channels, moving to other parts of the body. They circulate throughout the body until they find a favorable environment, like lung, bone, and brain, and create colonies of new tumors in these new locations. As an example, early in the course of breast cancer, some of the cells may move into the lymph nodes under the arm, which (in and of itself) is an indication of potential metastazing other tissues and organs in the body. This is the primary reason that many women who are diagnosed with breast cancer will also be asked to have one or more of the lymph nodes under their arms biopsied: to check for the presence of tumor cells there.
By comparison, benign tumors may grow quickly and to a very large size, but the benign cells will always remain in the same location where they first formed. Benign cells don’t move around; they never ‘hit the road’. Cancer cells, on the other hand, are on the move from Day One.
Third, cancer cells live forever. This is almost unimaginable, but it’s true. Cancer cells are virtually immortal. Normal cells don’t live forever. They are programmed to die. Programmed cell death (also called apoptosis) is part of nature’s master plan, and it actually works very well, for programmed cell death and its corollary, death of the organism, allows for evolutionary change and adaptation. And so, normal cells to die in order to make way for a new and improved cells, and eventually new and improved subsequent species.
Cancer cells have found the key to immortality by unhinging programmed cell death. How hard do you think it is, then, to catch up to immortality in a race for a cure? Really hard. Now you understand the difficulty patients and doctors face in eradicating this disease. Even one immortal cell left behind after surgery, radiation, chemotherapy, and targeted therapy is all that is required to set the whole malignant, catastrophic cycle of invasion and metastasis in to motion again. Cancer’s immortality renders it invincible unless doctors can find a way to kill every cancer cell, or otherwise prevent them from growing or moving around the body. This is really hard.
Now that you understand what cancer is, it’s nature and characteristics, you might ask, What causes cancer? What transforms a normal, law-abiding cell that knows its job and duty to die at the appropriate time, into a malignant, immortal renegade? When I started medical school in 1985, the favored explanation was that cancer cells arose from normal cells by way of genetic mutation. This is still the case; the question is, What sorts of mutations trigger invasion, metastasis, and immortality? Scientists believe that a single cell – that’s all it takes – is transformed by way of genetic mutations, and then grows indiscriminately, dividing and multiplying until its progeny have taken over the entire organism. This process whereby a single transformed cell leads to an empire of malignant renegades rampaging throughout the body is referred to as “clonal expansion”. It rests on the assumption that cancer formation takes place over the course of many smaller steps, from normal, to abnormal, to frankly malignant – all reflective of genetic changes that occur inside the cells.
As regards breast cancer, some researchers have recently discovered that cancer cells arise not from just any cell in the breast but from a particular type of cell in the breast called a stem cell. You may have heard of stem cells, for there is much controversy about them in regards to harvesting such cells from fetuses that have been aborted. But stem cells live in the human body as well. They live in the bone marrow, and some scientists believe there are stem cells that reside in the breast. Stem cells function like the National Guard; they are “on call” to be recruited when new cells need to be made, such as when the breast makes milk for a newborn child. Stems can undergo malignant transformation. Scientists now believe that the mutated stem cell sheds malignant cells in the same way that a machine gun fires bullets. And so, the malignant cells can then form a tumor, invade, metastasize, etc. This newer research is still under investigation, with not everyone yet buying into the theory of stem cell-driven cancer formation. But whatever the cause and source of the malignant transformation, the end result is a pack of unruly, misbehaving renegades that run wild throughout the body, changing and morphing by the day in ever more clever ways to avoid all attempts to kill or corral them, and having always on their side immortality as their ultimate weapon.
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