Prompted by an article about actress Olivia Hussey’s death, which mentioned that her breast cancer had “returned” ten years after her diagnosis and a double mastectomy. As a breast cancer survivor, I’ve long wondered, though, how, exactly, a cancer “returns”?
Let’s say a patient (not me) has a malignant tumor. The tumor is removed and enough of the surrounding tissue (of whatever type) for the surgeon to get clear margins. For this hypothetical, let us assume the margins are, indeed clear: the surgeon has “gotten it all.” The patient gets radiation, chemo, whatever the oncologist deems prudent. Five years later, the cancer returns. Where was it in the interim? Were there a few cancerous cells floating around somewhere that weren’t proliferating? Or was the cell “turned off” somehow so that it proliferated, but the cancer wasn’t active until the “switch” got flipped?
Or is it actually the same cancer? Do we use the term “returned” to mean “She got cancer again?”
As I understand it, if the cancer has not metasticized, i.e. spread outside the initial tissue, then clean surgical lines and no signs in lymph nodes suggest it is clear. After a set time, no recurrence means it is unlikely that remnants of the initial cancer were present to spread again.
Metastatic cancer is different. Once the cancer gets outside the initial tissue, it is systemic. Radiation and chemo are attempts to root it out, but unlikely to fully eradicate the cancer cells. The remaining ones are just small isolated units that avoid detection. Once those traces grow, they are considered a relapse.
“Returned” is a vague nontechnical term that can mean relapse or can mean a new case of a previous type.
From the National Institutes of Health — National Cancer Institute:
Although the article indicates that ‘recurrence’ is due to the presence of cancerous cells that “the first treatment didn’t fully remove or destroy” (presumably rendered temporarily incapable of rapid growth by the treatment), it is also possible for the same type of cancer to spontaneously develop again, especially cancers that arise from a defective gene or persistent environmental exposure (i.e. most common skin cancers, those from ‘occupational’ exposure to high levels of carcinogens, et cetera). Many types of cancer are also very difficult to completely eliminate; internal organ cancers (particularly pancreatic, intestinal, and liver cancers) can be treated with chemotherapy but they tend to be too broadly distributed for surgical invention and too crucial for aggressive treatments that could render the organ nonfunctional, so there is almost always some residual cancer cells requiring monitoring and potentially follow up treatment. Great improvements in efficacy have been made in treating some formerly very difficult to treat cancers, particularly common types of lung, breast, and renal cancers, Hodgkin’s lymphoma, many brain cancers, and in ovarian, cervical, and testicular cancers if they are caught early, to the point that they may not reoccur within the patients’ expected lifetime.
Unfortunately, when a type of cancer recurs (whether because of residual cancerous cells or a new incidence), it often becomes more difficult to treat, and frequently more aggressive in progression. On the other hand, the innovations in treating many common cancers are so much better that treatments are often easier to apply and cause less onerous side effects than previously available treatments, and the ability to target radiation treatments or precisely tailor chemotherapy doses can made treating even a more aggressive cancer easier to tolerate than treatments of even a decade or two ago.
“Late recurrences” of cancer are usually defined as occurring more than ten years after the original diagnosis.
We have poor understanding of just why some malignancies return after so long. It’s been suggested that stress may play a role.
This paper talks about how malignant cells from metastases that occurred before the primary tumor was discovered and resected may lie dormant for many years, either because they were removed from the cell cycle for whatever reason and stopped dividing, or lost a growth factor or other factor that permitted their spread.
Some types of malignancies (renal cell carcinoma is a notorious one) can return/recur after a long dormant period and pop up as mets in unlikely places
That’s just it: They haven’t. They might have gotten everything in the vicinity of the tumor, but the problem is that that wasn’t all of it. It’s already metastasized, and cells of that cancer are now spread throughout the body.
Cancers of the thymus, spleen, liver, some nasopharyngeal cancers, and of course lymphomas can recur because of cancer cells in the lymphatic system, but that isn’t true in general.
Metastasis is a different phenomenon than recurrence (or migration and invasive growth, although those are the precursor to metastasis). In recurrence, the cancer reappears in the original host tissue or organ. In metastasis, the cancer becomes free-floating cells that then express novel tropisms allowing them to occupy other tissues. Some types of cancer are particularly prone to metastasis while others stubbornly just grow in their original tissue for a long period of time; nobody really knows why although the predominate theory is that some cancers are more prone to producing multicellular clusters that are able to transport through the endothelium of blood or lymphatic vessels and survive long enough to embed in a new host tissue and start consuming nutrients.
Your distinction is not how I as a physician understand it, nor how the paper cited by @Jackmannii, titled “Cancer Metastases: Early Dissemination and Late Recurrences” uses the word.
No, recurrence does not exclusively mean within the original host organ or tissue. It can, and be a local recurrence, but there are also regional and distant recurrences.
When most of us, including clinicians, talk about a cancer recurring after years of being cancer free, we mean that the same cell line of cancer has shown up again anywhere in the body.
@Chronos is exactly right. Having clear margins and clear nodes does not always mean that there have not been any microscopic distant metastases. Those microscopic distant metastases can stay fairly inactive, quiescent, dormant, for years and then ramp back up (by a variety of mechanisms).
Some cancer types are more infamous of potential long dormant periods for those microscopic metastases than others.
To the specific of the OP breast cancer is on that list and for some types must be thought of as a chronic disease.
Risk factors for late recurrence include ER positivity, progesterone receptor positivity, and low Ki67. The most common sites of recurrence are the lungs/pleura and bones, which was also the case in our experience. It is no exaggeration to say that breast cancer is a chronic disease similar to hypertension and diabetes. This is because breast cancer is not completely cured by surgery alone and lasts for a long time, with patients requiring long-term hormone therapy. Moreover, it can recur even after 10 years or more.
When it is in the original tissue or organ the possibility of a new primary sometimes also gets raised pending exact cell line typing.
The section on “Tumour dormancy and reawakening” is interesting, and reviews both the mechanisms intrinsic to the cells that result in dormancy, and of the local environment in which growth does not get a chance to outpace cell death (mass dormancy). Really worth the read.
I stand corrected on the exclusion of metastasis from the definition of recurrence. But my essential point was that recurrence does not require metastasis, and while some cancers (such as many breast cancers) are often found of have metastasized upon recurrence, others recur in the original organ or tissue.
And when it is a local recurrence the question gets raised if it a “true recurrence” or “marginal miss” of the original cancer (same as with regional and distant recurrence - some cells were still there and were quiescent for a while, or took that long to grow to detectable size anyway), or if the recurrence is actually a new primary. I have limited knowledge here but my understanding is that treatment and prognosis can vary based on how that is determined. (Also to note that some same tissue/organ recurrence can be on the same and others on the opposite side, ipsilateral vs contralateral, and which one also has implications.) I think breast cancer local recurrences are more often new primaries than marginal misses or true recurrences, but am not sure. Anyone with real expertise please chime in!
Gene sequencing is reportedly a good method to separate new breast CA primaries from recurrence of a previous malignancy. More expensive and time-consuming than looking at characteristics like hormone receptors and Her-2/neu status, but also more reliable since ER/PR positivity/negativity can change as a tumor evolves (changes in HER-2/neu overexpression are less common).
And yes, separating new primaries from recurrences can be important in designing treatment and determining prognosis. De novo (“treatment-naive”) malignancies generally have a better prognosis.
I’d like to thank all of you, who are providing good information and cites here, for helping to educate me.
My mother has had breast cancer three times: initially in 1992 (at age 52), then a recurrence in 2008, and another recurrence in 2016. I’ve always wondered (and I don’t know if her doctors have entirely known) if the recurrences were the same cancer returning, or new malignancies.
I’ve read all the posts and the medical articles with great interest, and I’m deeply grateful for the information. Some of the information isn’t exactly reassuring, but then, I was looking fore explanations, not comfort.
My late wife was a BC survivor. Until she wasn’t. She was ER positive with a very slow-growing variant.
The initial ~1cm3 fairly nodular tumor was resected with clean margins and no lymph node involvement. Local radiation and hormone suppressive therapy followed the surgery.
11 years later with continuous monitoring her breasts were still clear but 3 small metastases were found elsewhere. The largest was just 2x4x4mm. By happenstance they all grew in areas where they could be detected at far smaller than typical sizes. Only the largest of the three could be biopsied or resected, and the path report was unequivocal: there was breast cancer growing in/on her scalp.
It certainly could not have originated there. And there was no sign of any tumors in her breasts, not then and not years later either. So it seems a betting certainty that this tumor’s progenitor cells had at some point broken off from the main tumor in her breast that had been removed over a decade before. And sat there as a slow time bomb until it was big enough to be noticed.
Eventually tumors blossomed all over her body despite suppressive therapies, both hormonal and cytotoxic. And eventually they overwhelmed her innards and she died. 25 years after the initial diagnosis and surgery.
My bottom line as an informed consumer of BC care, if not cancer care in general …
We can only detect tumors that are fairly big, comprising thousands if not millions of cells. The geometric growth rate suggests they can simmer along growing merrily for quite some time starting from single cells before they get to be a detectable agglomeration. And they may, depending on tumor type, be sloughing off cells to go voyaging around your body the whole time. Some of which may by happenstance find a suitable lodging spot and begin growing there. The slower the inherent growth rate of the cancerous cell line the longer this process takes to fully flower.