recurrence patterns
I have been wondering if there are any statistics regarding recurrence patterns. When do most recurrences happen? In the first 5 years? 10 years? Or is it all just a crap shoot? Do treatment choices change recurrence patterns? I know that mastectomy has a lower recurrence percentage than lumpectomy, which makes sense as there isn't as much breast tissue left. And radiation and hormone therapy reduce percentages too. I am not really asking about recurrence percentages or likelihood of recurrence. More curious of when they happen if they do. Is there a difference between ER/PR negative recurrence timeline vs positive ER/PR?
I am 3/1/2 yrs post diagnosis. All good so far. I was so terrified at first but things have settled down. I no longer am obsessed with recurrence issues but lately have given thought to what I wrote above. Maybe the thoughts about recurrence never go away completely....
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DCIS recurrences can happen within the first few years, or 20 years later. To my understanding, recurrence patterns vary based on the aggressiveness of the DCIS; a high grade DCIS with comedonecrosis will be more likely to recur sooner, whereas a low grade DCIS might not recur for many years. According to the following study, recurrence rates also differ for those who had rads vs. those who didn't:
https://www.ascopost.com/issues/june-15-2011/radiotherapy-in-dcis-recurrence-patterns-are-different/
The following study provides some more general information about DCIS recurrence rates, and includes a comparison of DCIS recurrence rates, over time, with and without rads and hormone therapy: https://current-oncology.com/index.php/oncology/article/view/1892/1523
One thing to keep in mind is that in addition to the recurrence risk, anyone diagnosed one time is at greater risk to be diagnosed a second time. This would be a new primary DCIS or invasive cancer, not a recurrence, and unrelated to the first diagnosis. Like all women, our risk to develop breast cancer is highest when we are in our 60s and 70s, so similarly, the risk to develop a second primary breast cancer would be greatest when we are in those decades of life. This second primary could occur in either breast.
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I was curious if recurrences after having DCIS are similar to having recurrences after invasive. For example, TNBC has a higher occurrence rate the first several years compared to ER/PR positive BC (that is my understanding). Then from what I have read the occurrence rate actually drops lower as the years go by. This is of interest to me because I had ER/PR negative (HER not tested) grade 3. Think that puts me on the more aggressive DCIS side. It was so hard to not worry in the beginning. But I've got a few years under my belt now and I would love to be able to think that as time goes by the risk of recurrence will dwindle. Of course getting older raises the risk, I understand that, not just for BC buy for all sorts of ailments. I don't know....maybe it is all just a crap shoot.
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Beesie -- thank you for posting those links. Interesting and informative reading. I'm curious, have they done studies like these on IDC/ILC? I had DCIS and IDC so I'd love to read any info about the other half if you know where I could find it.
Thanks in advance.
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Bumping this thread...
I am really frusterated about this. My oncologist told me I could consider my selves healthy 5(!) years after the mastectomy (if still NED).
But why? I have read that 50% of recurrences in hormonesensitive breast cancer comes later than 5years after...
Do stage, grade, lymphstatus have anything to say???
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You already seem to know a good amount about recurrence risk factors and rates but predictions are so difficult, especially now. Just a few years ago it was still believed that cancer started in the breast, moved to lymph nodes and metastasized from there but recently it’s been discovered that it can bypass lymph nodes and go from tumor to the blood stream, even from small tumors, once considered less threatening. I read somewhere about research on this but I think it’s just getting started. In my case, my tumor metastasized before I ever felt the lump, unfortunately we’re still learning how it behaves. Good luck 🙂
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Anna - Here are a few links explaining a bit about what Illimae pointed out in her post.
Plus, Kkubsky, here a "few" studies I found while Googling "recurrence patterns". Thanks for posing the question. I had often wondered about this all myself, but never imagined there would actually be studies published on them. Does seem to be a connection in some areas, while not in others. Also, younger age, again seems to factor in.
Made for illuminating reading, definitely learned a few things.
Hope this helps you out in your own journeys.
Research Worth Watching: Overview From San Antonio 2018 Conference
"When I started as a breast surgeon, we believed that after a cancer started growing in the breast, it slowly moved from one lymph node to another and then, after invading all the nodes, went into the blood stream, where it traveled to other parts of the body. We thought if we got there soon enough, and did a big enough surgery, we could slam the door before the migration to the nodes and blood stream began.The role of surgery and the value of mastectomy in breast cancer treatment has significantly diminished
Now we understand that most, if not all, breast cancers have sent cells out into the blood stream way before we are able to diagnose the disease. Up to 40 percent of breast cancer patients have detectable disseminated tumor cells already in their bone marrow at the time of diagnosis. The fact that we can find these circulating tumor cells (CTCs) in the blood or disseminated tumor cells (DTCs) in the bone marrow at the time a person is first diagnosed with an early-stage breast cancer shows that what we have termed early detection is not really very early."
Early dissemination seeds metastasis in breast cancer
"Cells from early, low-density lesions displayed more stemness features, migrated more and founded more metastases than cells from dense, advanced tumours. Notably, we found that at least 80% of metastases were derived from early disseminated cancer cells. Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination."
Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications
"For Some Solid Tumors, Including Cutaneous Melanoma and Breast Cancer, Orderly Progression From Local Tumor Growth at the Primary Site to the Sentinel Lymph Node (SLN) and Regional Lymph Nodes (Non‐SLN Compartment) Occurs, Followed by Dissemination to Distant Sites Through the Blood and Bone Marrow. Occasionally (15%‐20% of the time), micrometastatic cancer cells may bypass the lymph nodes and spread to distant sites directly. Thus, tumor dissemination through the lymphatic route from the primary site may serve as a working hypothesis. Certainly, this is not a general rule and exceptions are discussed in the text."
"It is important to note, however, that approximately 15% to 20% of the time, cancer cells can spread 1) simultaneously via the lymphatic channels to the SLNs and vascular channels to the distant sites or 2) to the systemic sites alone via the vascular system (Fig. 1). In cutaneous melanoma, follow‐up of large series of patients with negative SLNs has demonstrated that in the approximately 10% of those who develop recurrence after WLE of the primary site and SLN excisional biopsy, 50% will manifest disease at distant sites.58, 59 This suggests that there is indeed a subset of patients in whom disease progression "skips" the SLN completely. In patients with breast cancer, Chia et al reported on 10‐year outcomes of over 1000 patients with lymph node‐negative disease and who did not receive systemic therapy.60 The authors found that 10% to 25% of these patients had first recurrence at distant sites, with a higher frequency noted in those patients with larger‐size tumors. More recent reports using other databases of lymph node‐negative, medically untreated patients with breast cancer (Rotterdam, TRANSBIG, and MAINZ) have suggested that up to 20% to 30% will develop distant metastasis by 5 years.61, 62"Pathways of parallel progression
https://www.nature.com/articles/nature21104#ref2
"Two studies in mice identify mechanisms by which tumour cells disseminate in very early breast cancer. Both show that these cells colonize distant tissues more efficiently than their later counterparts. See Article p.552 & Letter p.588"
"The first compelling data to call the linear-progression model into question came from studies of human breast cancer. Genetic analysis of primary breast tumours and corresponding DCCs showed that, at the time of tumour detection, DCCs had fewer genetic alterations than primary cells, implying that DCCs seed the bone marrow early in disease progression, and evolve separately2. This theory of parallel progression5 was supported by the revelation that 20–30% of patients classified as having 'non-invasive' breast cancer have DCCs in their bone marrow7,9. Because up to 8% of 'non-invasive' breast cancers recur at distant sites12, it was assumed that at least some of these early DCCs had metastasis-initiating potential."
From latent disseminated cells to overt metastasis: Genetic analysis
https://www.pnas.org/content/100/13/7737
Evaluation of recurrence patterns and survival in modern series of young women with breast cancer
"The data on oncologic outcomes in young women with breast cancer (BC) are dated as it relates to recurrences and mortality. Our goal was to assess these outcomes in a modern series of young women with BC. A retrospective chart review identified women ≤40 years old with stage I‐III BC diagnosed from 2006 to 2013 at our institution. Demographics, tumor biology, type of operation, recurrence, and survival were analyzed. Overall, 322 women were identified. Most had ER+(70%) infiltrating ductal tumors (88%) with low stage (42% T1; 41% T2; 56% N0). Follow‐up was 4.2 years with 5.6% local‐regional recurrence (LRR), 15.2% metastatic recurrence (MR), and 8% mortality. There was no survival difference based on demographics, tumor biology, or type of operation. T3 tumors (P < .001) and node positivity (P < .001) were associated with worse disease‐free survival. In this modern series of young women with BC, stage rather than tumor biology or surgical choice has more effect on recurrence‐free survival. MR was more common than LRR, with most MR occurring within the first 2 years after surgery."
Evaluation of Local and Distant Recurrence Patterns in Patients with Triple-Negative Breast Cancer According to Age
"Among 1930 patients with TNBC, 289 (15 %) were <40 and 1641 (85 %) were ≥40 years of age at diagnosis. Younger patients were more likely to present with higher stage disease and more likely to receive mastectomy (p < 0.01), axillary node dissection (p < 0.01), and chemotherapy (p < 0.01). At a median follow-up of 74 (0-201.1) months, there was no difference in LR or disease-free survival (DFS) by age group [5-year LR = 3.9 % (95 % confidence interval (CI) 1.5-6.2) vs. 4.5 % (95 % CI 3.5-5.6) and 5-year DFS = 75.3 % (95 % CI 70.2-80.7) vs. 77.7 % (95 % CI 75.6-79.8), p = 0.94] in patients aged <40 and ≥40 years, respectively. On multivariate analysis, larger tumor size, lymphovascular invasion, and nodal positivity were associated with increased risk of DR. Age and type of surgery were not significantly associated with either outcome.
CONCLUSIONS:
Young age at diagnosis is not an independent risk factor for LR or DR in patients with TNBC."
Biological Subtypes and Distant Relapse Pattern in Breast Cancer Patients After Curative Surgery
"Previous studies have demonstrated significant differences in terms of DFS and OS [17,23,29,30]. The luminal A group had better results in these studies and their results are consistent with our data. Patients with bone metastases have better OS than those with visceral metastases [23,31]. Examining metastatic sites in detail on an individual basis, it was observed that results vary across biological subgroups. Similar to the current study (66.2% and 53.9% in luminal A and B vs. 45.1% and 38.9% in triple-negative and HER2-overexpressing groups), bone metastases in previous studies were more frequent among patients with luminal subgroup than in others [17,18,19,23]. Liver was the most common site of first metastases among HER2-overexpressing patients in both previous and our current studies. Again, previous studies and our study suggest that compared with the other biological subtypes, luminal A patients rarely experienced lung metastases as first site [17,18,19,23]. Triple-negative and HER2-enriched subgroups were predominant for brain metastases compared with luminal groups [17,18,19,23]. Sihto et al. [19] reported that breast cancer patients with basal type had the first distant metastases at multiple sites more frequently than patients with other subtypes (50% vs. 26.9%, p = 0.015). In our study, the rate of first distant metastases at multiple sites was more common among HER2-enriched and triple-negative groups than in luminal groups (40% vs 33.9%, p = 0.028).
In conclusion, this study demonstrates that the biological subtypes in breast cancer are not only distinct in terms of primary tumor characteristics and aggressiveness, but also differ in terms of their ability to metastatize to distant organs. These data can provide useful information for surveillance."
Patterns of Early Recurrence (Early Recurrence Risk: Aromatase Inhibitors versus Tamoxifen, Emilio Bria)
"Although a peak of overall breast cancer recurrences was previously reported during the first 2 years after surgery in patients receiving adjuvant therapy,[4] the type of recurrence was not defined. This peak remained when patients were stratified according to known breast cancer recurrence risk factors; patients with larger tumors and increased nodal involvement had higher risks for overall recurrence, but the risk again peaked during 2–3 years after surgery.[4] In another study (n = 2509), 456 patients relapsed (18%), over half (58%) in the first 3 years following the primary operation and the majority (79%) during the first 5 years.[6]These findings identify the first 2–3 years after surgery as a key interval for breast cancer recurrence and highlight the need for preventive measures using adjuvant hormonal treatment."
"A more recent study examined the pattern of breast cancer recurrence in women (n = 3614) with ER-positive EBC receiving adjuvant tamoxifen, the standard of care prior to the introduction of the AIs.[5] A total of 476 patients (13.2%) had recurrences during the median 5-year follow-up, and analysis of recurrence rates identified a peak of overall recurrence at year 2.0 and between years 3.5 and 4.0."Patterns and predictors of first and subsequent recurrence in women with early breast cancer
"The risk of first recurrence was highest during the second year post-diagnosis (3.9%; 95% CI 3.5–4.3) with similar patterns for LR, RR and DM. Young age (<40), tumour size >2 cm, tumour grade II/III, positive lymph nodes, multifocality and no chemotherapy were prognostic factors for first recurrence. The risk of developing a second recurrence after LR or RR (N = 176) was significantly higher after RR than after LR (50 vs 29%; p < 0.001). After a second LR or RR, more than half of the women were diagnosed with a third recurrence. Conclusions: Although the risk of subsequent recurrence is high, absolute incidence remains low. Also, almost half the second recurrences are detected in the first year after previous recurrence and more than 80% are DM. This suggests that more intensive follow-up for early detection subsequent recurrence is not likely to be (cost-)effective."
Long-Term Risk of Breast Cancer Recurrence After 5 Years of Endocrine Therapy
https://www.ascopost.com/News/58288
"After adjustment for TN status, tumor grade and Ki67 status were of moderate independent predictive value for distant disease recurrence, whereas progesterone receptor status and HER2 receptor status were not predictive. During the 5 to 20 years of follow-up, the absolute risk of distant disease recurrence among patients with T1, N0 breast cancer was 10% for low-grade disease, 13% for moderate-grade disease, and 17% for high-grade disease, with a corresponding risk of any recurrence or contralateral breast cancer being 17%, 22%, and 26%, respectively.
The investigators concluded: "After 5 years of adjuvant endocrine therapy, breast-cancer recurrences continued to occur steadily throughout the study period from 5 to 20 years. The risk of distant [disease] recurrence was strongly correlated with the original TN status, with risks ranging from 10% to 41%, depending on TN status and tumor grade."
"Dr. Pan emphasized the "effect of the additive T+N score" on outcomes, noting that almost 50% of patients with T2N2 (4–9 nodes) disease suffered a recurrence by year 20.
The analysis calculated the following relative risks: for one to three positive nodes, vs negative nodal status, 2.08; for T2N0 vs T1N0, 1.73; for high vs low grade for T1N0 disease, 2.02; for Ki67 > 20% vs 0%–13%, 1.63.
Conversely, in all women (any T/N status), lower risk in years 5 to 20 was predicted by low vs moderate/high grade (adjusted relative risk [RR], 0.7) and Ki67 0%–13% vs ≥ 14% (RR, 0.7). Positive progesterone receptor status was not predictive; there were no data on genotype; and age had little value as a predictor, except for in women younger than 40, who had a 40% increased risk of distant recurrence, revealed Dr. Pan.
Similar associations were seen for breast cancer mortality, but contralateral cancer rates (0.3%/year) were essentially unrelated to these risk factors, he added. "
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Thanks, Spoonie, for all the great information and links.
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Glad to help, MountainMia. That's one of the things thatI love about this community - learning together. Makes us stronger.
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Thank you for lots of good informations!
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A new research article came out - thought I'd share here since we've been discussing this topic.
Mixed Results for Profiling in Predicting Late Recurrence in ER+ Breast Cancer (published 07/2/2019)
"Late recurrences, defined as happening 5 or more years after diagnosis, account for at least half of all recurrences in estrogen receptor (ER)-positive, early-stage breast cancer. Tumor size and nodal status predict for recurrence, even after 5 years. Data from the Early Breast Cancer Trialists' Collaborative Group Meta-Analysisdemonstrated that breast cancer recurrences continued steadily from 5 to 20 years in women younger than age 75 at diagnosis of ER-positive breast cancer who were disease-free after 5 years of scheduled endocrine therapy.The projected risk of distant recurrence 20 years from diagnosis was 13% among the patients with N0T1 disease (i.e., size smaller than 2 cm) and 19% in those with N0T2 cancer. In the modern era, with improved treatments, the rates of distant recurrence are probably lower, although it will take longer follow-up to define this risk precisely."
"Circulating Tumor Cells
In the follow-up phase, circulating tumor cells (CTCs) were associated with late recurrence in a substudy of the E5103 study, a phase III trial of adjuvant doxorubicin plus cyclophosphamide plus paclitaxel with or without bevacizumab. In the substudy, 547 patients with stages II-III breast cancer without evidence of recurrence had a one-time blood draw for CTCs 4.5 to 7.5 years after surgery. Positive CTCs were defined as at least one CTC per 7.5 mL of blood, and 26 of the patients (4.8%) had evidence of CTCs. Positive CTCs were more common in high-grade, node-positive, larger tumors, the researchers reported.
In addition, 23 of the 353 ER-positive patients (6.5%) and one of 193 ER-negative patients (0.5%) had a recurrence. Seven of the 23 (30.4%) ER-positive patients with recurrence had positive CTCs. CTC positivity was associated with a 13-fold higher risk of clinical recurrence compared with CTC negativity, and positive CTCs were not associated with recurrence in the patients with ER-negative breast cancer.
A positive association between CTC burden and recurrence was found in ER-positive patients: the rate of recurrence was 4.8% in patients with no CTCs per 7.5 mL, 16.7% in those with one CTC per 7.5 mL, and 83.3% in those with two or more CTCs per 7.5 mL."
"Also speaking at SABCS, Julie R. Gralow, MD, director of Breast Medical Oncology at the University of Washington in Seattle, noted that a translational substudy of the SUCCESS A trial examined CTCs before and 2 years after chemotherapy in 1,087 patients with node-positive or high-risk node-negative breast cancer. At the 37-month follow-up, the presence of CTCs was associated with decreased overall survival (OS) and disease-free survival (DFS). The hazard ratio (HR) for OS was 3.91 and for DFS, 2.31, in the CTC-positive versus CTC-negative patients.
"Interestingly, the prognostic value of CTCs 2 years after the end of treatment differed by tumor type," Gralow said. "The luminal A, luminal B, and triple-negative CTCs were prognostic."
She explained that several small studies suggest that circulating tumor (ct) DNA can predict disease progression and relapse, and although some ctDNA assays have demonstrated clinical validity or utility with certain types of advanced cancer, evidence is insufficient for most of the ctDNA assays, and there has been some discordance of results of the ctDNA assays and genotyping tumor specimens, according to a joint review by ASCO and the College of American Pathologists.
Studies of the circulating serum proteins MUC-1 and CEA have shown that they can detect asymptomatic recurrent breast cancer.
The question with these assays, said Gralow, is whether they are predicting late recurrence or detecting actual asymptomatic recurrence or reactivation of the cancer."
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If I am reading this correctly, at 5 years your tumor markers tests should be 0?? Or you are higher risk of DR after 10 years?? I really don’t understand this study, Most TM tests are 0-25 as normal or considered OK?
Help me understand
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The numbers are not favorable to ER positive folks. I am very disappointed yep, I know I will never get rid of it.
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Barteeellis
It is my understanding that CTCs are circulating tumour cells. The CTC test is an entirely different test from tumour markers tests. Tumour markers do not need to be 0.
Most recurrences happen within first 5 years but late recurrence can happen particularly for Hormone positive cancers. Your risk doesnt get higher after 5years, but it doesnt drop off drastically either. CTC tests can be prognostic factors for reoccurrence but they are not standard tests at present.
Hope that helps explain it somewhat.
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Assuming 50% of recurrences happen in the first 5 years and the other 50% in the years 5 and beyond, this still makes the the first 5 years the highest risk for recurrence. I see this fact repeatedly comes up on this board and some mistakenly think that risk never goes down or it's higher in years 5+. Risk does gradually go down, it just never goes away.
Let's say there are 100 recurrences in a given population, this means that 50% recur in years 0-5, that is roughly 10 per year for argument's sake, although it's not an equal distribution and highest risk is still years 2-3.
The other 50 events happen from years 5 until the time all women die (of all causes), not knowing that number, I think it's safe to assume it's decades. So the remaining 50 events are divided to 20-30, which makes it significantly less than 10 per year of the first 5 years, again the distribution would be highest in the years 5-10.
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If I get a recurrence, let it be after I’m dead.
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hahahahhaha. My feelings exactly.
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ErenToo - this might clarify what you were getting at I think (had posted this earlier in the thread)
Patterns of Early Recurrence (Early Recurrence Risk: Aromatase Inhibitors versus Tamoxifen, Emilio Bria)
"Although a peak of overall breast cancer recurrences was previously reported during the first 2 years after surgery in patients receiving adjuvant therapy,[4] the type of recurrence was not defined. This peak remained when patients were stratified according to known breast cancer recurrence risk factors; patients with larger tumors and increased nodal involvement had higher risks for overall recurrence, but the risk again peaked during 2–3 years after surgery.[4] In another study (n = 2509), 456 patients relapsed (18%), over half (58%) in the first 3 years following the primary operation and the majority (79%) during the first 5 years.[6] These findings identify the first 2–3 years after surgery as a key interval for breast cancer recurrence and highlight the need for preventive measures using adjuvant hormonal treatment."
"A more recent study examined the pattern of breast cancer recurrence in women (n = 3614) with ER-positive EBC receiving adjuvant tamoxifen, the standard of care prior to the introduction of the AIs.[5] A total of 476 patients (13.2%) had recurrences during the median 5-year follow-up, and analysis of recurrence rates identified a peak of overall recurrence at year 2.0 and between years 3.5 and 4.0."Patterns and predictors of first and subsequent recurrence in women with early breast cancer
"The risk of first recurrence was highest during the second year post-diagnosis (3.9%; 95% CI 3.5–4.3) with similar patterns for LR, RR and DM. Young age (<40), tumour size >2 cm, tumour grade II/III, positive lymph nodes, multifocality and no chemotherapy were prognostic factors for first recurrence. The risk of developing a second recurrence after LR or RR (N = 176) was significantly higher after RR than after LR (50 vs 29%; p < 0.001). After a second LR or RR, more than half of the women were diagnosed with a third recurrence. Conclusions: Although the risk of subsequent recurrence is high, absolute incidence remains low. Also, almost half the second recurrences are detected in the first year after previous recurrence and more than 80% are DM. This suggests that more intensive follow-up for early detection subsequent recurrence is not likely to be (cost-)effective."
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Thanks, spoonie
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I have a question about luminal B subtype. My BS told me this is my type, but I have a low Ki-67. I think I saw 1 scholarly article that said B's are high Ki-67 OR PR-/low PR. Now I can't find the article. Did I imagine it? I'm starting to wonder why BS said I'm a B.
My Ki-67 is only 5% - 10%, same with my PR+.
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Maybe there is some other criteria that your BS took into consideration? As far as I am aware Luminal B is usually Her+ or Er + Pr+ with high Ki67 or Er+ Pr -. Although you can still be Luminal A with Er+ and Pr- with low ki67. You definitely dont fall under standard Luminal B. I would be interested to find out why your BS categorized you in that way, should you decide to ask and are willing to share.
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bump
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Bumping for new members
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uggghh- I missed this one the first time around. According to that chart- with a T2n1 and being under 40 at diagnosis, that puts me at a 40% (29 plus additional 40%) chance at 20 years. Makes me sick. I had a weird tumor with low grade but high-ish ki67, I think it was 17. Also PABC (pregnancy associated bc) which I didn't even know was a thing, but it doesn't have good stats. Anyway, just gotta keep living, making it count, right? I had a rough idea about these numbers, I just try to put them in a box and ignore them mostly.
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bumping
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Spoonie,
What is TN? What is ki67?
Thank you,
JCP
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CPeachyMom,
What is TN or ki67?
I'm trying to figure it out.
Thank you,
JCP
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TN is triple negative - that is, Estrogen negative, Progesterone negative and HER2 negative. You might see it abbreviated as ER/PR/HER2. I don't know about the other
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Imagine,
I was wondering how did you find out about the lungs. I am going for a ct next week.
Any information is appreciated.
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Thank you!
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Thank you spoonie77 for the most excellent post.
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