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Jun 24, 2019 01:10AM
Jun 24, 2019 02:13AM
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 The role of surgery and the value of mastectomy in breast cancer treatment has significantly diminished
"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.
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
"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
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.  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, 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. 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. 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. 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
"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."
EBCTCG Analysis Identifies Recurrence Risk by Tumor Subgroup in Estrogen Receptor–Positive Breast Cancer
"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. "
"Spoonie" who entered BC World @ 41. DXd w/MS & Thyroid Cancer @42. Treatment: LX/SLNB/RADs. Plan A: 5mg Tamox = 0 QOL. Plan B: OS/AI = Rare allergy to OS meds. Plan C: Only option left, Diet & Exercise. PS: Not a dr, just a Googler.
7/20/2018, IDC, Left, 3cm, Stage IIA, Grade 2, 0/3 nodes, ER+/PR+, HER2- (FISH)
8/30/2018, DCIS, Left, 1cm, Stage 0, Grade 2
8/30/2018 Lumpectomy: Left; Lymph node removal: Left, Sentinel
10/1/2018 Whole-breast: Breast, Lymph nodes, Chest wall
3/30/2019 Tamoxifen pills (Nolvadex, Apo-Tamox, Tamofen, Tamone)
7/2/2019 Zoladex (goserelin)