Why Receptor Status Matters
Breast cancer is not a single disease, and researchers now have the ability to break down breast cancer into different subtypes based on the receptor status of the tumors. Among the variations between different types of breast cancers are the proteins found on cell surfaces, which are involved tumor growth. These proteins are related to the genetic material of cancer cells.
For example, with estrogen receptor-positive breast cancer, estrogen binds to specific receptors on breast cancer cells, stimulating proliferation. Similarly, HER2 receptors on the surface of breast cancer cells are stimulated by HER2 protein, promoting the growth and spread of breast cancer.
Its important to note, however, that all breast cellsboth cancerous and noncanceroushave HER2 receptors on their surfaces. The difference is that HER2-positive breast cancer cells have 40 to 100 times more receptors than HER2-negative breast cancer cells or normal breast cells. In positive cases, the abundance of receptors fuels the cancer.
Breast Cancer Discussion Guide
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Survival Rates For Breast Cancer
Survival rates can give you an idea of what percentage of people with the same type and stage of cancer are still alive a certain amount of time after they were diagnosed. They cant tell you how long you will live, but they may help give you a better understanding of how likely it is that your treatment will be successful.
Keep in mind that survival rates are estimates and are often based on previous outcomes of large numbers of people who had a specific cancer, but they cant predict what will happen in any particular persons case. These statistics can be confusing and may lead you to have more questions. Talk with your doctor about how these numbers may apply to you, as he or she is familiar with your situation.
Tumour Size Nodal Status And Tnm Stage
Pathologic T and N status was coded according to AJCC 4th edition for 20052008 and AJCC 6th edition for 20082015 and categorized as pT1 , pT2 , pT3 , pT4, pN0 , pN1 , pN2 , pN3 and pN+ , and combined as pT1pN0, pT2pN0, pT1-2pN+ and pT3-4pN0/+ according to Norwegian treatment guidelines. Patients receiving neoadjuvant treatment were missing pTN status. Pathologic TNM stage was categorized into I, IIA, IIB, IIIA, IIIB or IV . This was combined with a SEER summary stage variable based on clinical data when pTNM missing into a TNM stage variable .
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Regional Relapse Following Breast Cancer Treatment Carries A Poorer Prognosis
Most localized breast cancers are treated by either breast conserving surgery with radiation therapy, or by mastectomy.
A medical study from 2010 estimates that around 40% of all women with breast cancer will suffer a recurrence.
The prognosis following a breast cancer recurrence is influenced by a number of factors. These include:-
- The Disease Free Interval: This is the time elapsed from diagnois and treatment of the first breast cancer to the recurrence
- The location of the recurrence: Whether the recurrence is in the same breast , or if it recurs in the contralateral breast, regional lymph nodes, or the chest wall .
Patients with breast cancer relapses are typically generally treated with either a salvage mastectomy, or radiation to the chest wall, regional lymph nodes, or both.
Systemic therapy may be implemented at this point. However, this will be determined on an individual basis, based on the likelihood of distant metastasis, characteristics of the tumor, and other factors.
Age And Stage For Breast Cancer Survival
Research over the years has generally shown that women under 40 years have a poorer than average prognosis. Interestingly, this factor is particularly relevant when the breast cancer is axillary node negative.
A medical study published in 2015 examined 4,453 Swedish women diagnosed with invasive breast cancer between 1961 and 1991 regarding age at diagnosis.
This research showed that women under 40 years had a higher mortality rate both for 5 year and 10 year survival rate.
However, older ladies between ages 70 and 79 and over 80 years had a higher mortality rate in both the 5 and 10 year follow up periods. The statistically worst outcome, after all adjustments for other factors, is for ladies over 80 years.
Furthermore, an earlier taken from SEER statistics between the years of 1988 to 2003 found that women under 40 years had lower rates of survival for stage I and II breast cancers.
Conversely, younger women tended to have a more favourable chance of survival at stage III and IV compared with those over 70 years of age.
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Mechanisms Of Breast Cancer Metastasis
No one really knows what factors will make a certain patient more or less susceptible to breast cancer metastasis.
There is growing awareness that part of that susceptibility is due to host factors. The host factors are the characteristics of the non-malignant cells and the general biological environment surrounding the malignant breast tumor.
Sometimes the host factors are referred to as the pre-metastatic niche and it is thought that bone-marrow-derived progenitor cells may directly influence the dissemination of malignant cells to distant areas.
Non-neoplastichost cells within the tumor may also play a key role in the regulation of breast cancer metastasis.
What Are Symptoms Of Triple Negative Breast Cancer
TNBC symptoms are the same as other common breast cancers. And many breast cancer symptoms are similar to other less serious conditions. That means having certain symptom doesnt mean you have breast cancer. Possible breast cancer symptoms include:
- A new lump or mass.
- Swelling in all or part of a breast.
- Dimpled skin.
- Nipple retraction, when your nipple turns inward.
- Nipple or breast skin thats dry, flaking, thickened or red.
- Nipple discharge that is not breast milk.
- Swollen lymph nodes. This symptom happens when breast cancer spreads to the lymph nodes under your arm or near your collarbone.
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What Are The Chances Of Breast Cancer Recurring
Despite huge advancements in breast cancer screening, early detection and treatment, a percentage of breast cancers will recur and spread to distant sites.
Although at the moment, it is almost impossible to say which cancers will recur and at what time period from diagnosis, there are a few factors that are known to increase the risk for recurrence.
These risk factors include:-
- Lymph node involvement and number of lymph nodes affected at the time of diagnosis
- Tumor Size at the time of diagnosis
- A subtype of Breast Cancer and hormonal receptor Status
- The time span from the initial diagnosis to recurrence of breast cancer
The Overall Prognosis For Her
Many studies demonstrate that breast cancers with an over-expression of HER-2 have a poorer prognosis. It is difficult however to isolate just the HER-2 aspect of the tumor as the specific cause of this poorer outlook.
In addition, it is difficult, in general, to find practical indications of just what a negative prognosis actually means.
The HER-2 status is part of the picture, but so are:-
- tumor size
- grade
- lymph node status
- Other hormonal indicators
- the type of cancer
However, it is clear that a positive HER-2 over-expression does correspond to an increase in the likelihood for lymph node metastasis.
HER-2 over-expression can also predict a poorer response to Taximophen , though researchers are working on ways to combat this.
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Chemokine Receptor Specific Findings
ACKR1/DARC
CCR3
The CC Motif Chemokine Receptor 3, CCR3, is expressed in eosinophils, basophils, T, NKT, and airway epithelial cells. It may contribute to accumulation and activation of eosinophils and other inflammatory cells. CCR3 has been associated with improved relapse-free survival in breast cancer with high expression of CCR3 in luminal-like rather than triple negative or HER2enrichedtumors. Our results for the breast TCGA cohort show that CCR3 is higher in the triple negative subtype than in luminal A and B . In addition, we found CCR3 was upregulated in luminal A, HER2 enriched, and triple negative tumors of only Black versus White patients.
CCR6
The CC Motif Chemokine Receptor 6, CCR6, is expressed by immature dendritic cells and memory T cells. The ligand of this receptor is macrophage inflammatory protein 3 alpha . CCR6 is highly expressed in pro-tumorigenic macrophages within the mammary gland microenvironment, promoting breast cancer tumors. CCR6 was differentially expressed, being down regulated in Asian versus White and in Black versus White patients . High expression of CCR6 significantly associated with worse overall breast cancer patient survival , but correlated with better survival in basal and HER enriched patients . We found CCR6 is higher in luminal A and in triple negative than in luminal B breast cancers. We also found higher CCR6 expression in Black versus White patients with luminal A molecular subtype breast tumors.
CCRL1
CCRL2
CXCR1 and CXCR2
Treatment Options For Her2 Positive Breast Cancer Tumors
Treating doctors will usually offer women with HER-2 positive breast treatment with Trastuzumab .
Indeed, this is the only therapy that the US Food and Drug Administration approvesfor women with breast cancer tumors over-expressing HER-2 proteins.
It is often the case that women with HER2 breast cancer tumors do not respond to Tamoxifen therapy.
But, the use of trastuzumab in combination with chemotherapy has led to longer survival rates for women with metastatic HER-2 positive breast carcinomas.
The addition of Herceptin when HER-2 is positive gives an amazing boost to the response and cure rates.
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Expert Review And References
- American Cancer Society. Breast Cancer. 2015: .
- de Boer M, van Dijck JA, Bult P, Borm GF, Tjan-Heijnen VC. Breast cancer prognosis and occult lymph node metastases, isolated tumor cells, and micrometastases. Journal of the National Cancer Institute. Oxford University Press 2010.
- Lonning PE. Breast cancer prognostication and prediction: are we making progress?. Annals of Oncology. Oxford: Oxford University Press 2007.
- Morrow M, Burstein HJ, and Harris JR. Malignant tumors of the breast. DeVita VT Jr, Lawrence TS, & Rosenberg SA. Cancer: Principles and Practice of Oncology. 10th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins 2015: 79: 1117-1156.
- Tripathy D, Eskenazi LB, Goodson, WH, et al. Breast. Ko, A. H., Dollinger, M., & Rosenbaum, E. Everyone’s Guide to Cancer Therapy: How Cancer is Diagnosed, Treated and Managed Day to Day. 5th ed. Kansas City: Andrews McMeel Publishing 2008: pp. 473-514.
Are There Any Statistics On Recurrence Rates Or Incidence Of Metastasis
As mentioned, it is very difficult to find statistics on metastatic breast cancer that has recurred after initial diagnosis. However, these cases represent a large proportion of Stage IV breast cancer cases and overall deaths.
Most of the statistical data on Stage IV or metastatic breast cancer is from those women presenting at diagnosis. According to the Metastatic Breast Cancer Network in 2012 new cases of Stage IV breast cancer were between 13,776 to 22,096.
The number of breast cancer recurrences at Stage IV is estimated to be between 20% and 30% of all breast cancer diagnoses.
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How To Prevent Breast Cancer
There is no guaranteed way to prevent breast cancer. Reviewing the risk factors and modifying the ones that can be altered can help in decreasing the risk.
Following the American Cancer Society’s guidelines for early detection can help early detection and treatment.
There are some subgroups of women that should consider additional preventive measures.
- Women with a strong family history of breast cancer need genetic testing such as HER2-Positive and BRCA Gene tests. Discuss this with a health care provider and meet with a genetic counselor who can explain what the testing can and cannot tell and then help interpret the results after testing.
- Chemoprevention is the use of medications to reduce the risk of cancer. The two currently approved drugs for chemoprevention of breast cancer are tamoxifen and raloxifene , which also blocks the effect of estrogen on breast tissues. Their side effects and whether these medications are right for an individual need to be discussed with a health care provider.
- Aromatase inhibitors are medications that block the production of small amounts of estrogen usually produced in postmenopausal women. They prevent reoccurrence of breast cancer but are not approved at this time for breast cancer chemoprevention.
- For a small group of patients who have a very high risk of breast cancer, surgery to remove the breasts may be an option. Although this reduces the risk significantly, a small chance of developing cancer remains.
Gene Expression Based On Clinical Parameters
We used RNA-seq HTSeq-counts and clinical sample data from the TCGA breast cancer patients, accessed through the GDC portal. Box and whisker plots represent the interquartile range and median line with a Log10 axis scale showing RNA-seq HTSeq-counts with global significance for ANOVA with Kruskal Wallis.
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De Novo Metastatic Breast Cancer And Recurrent Breast Cancer
It is important to understand the two types of Stage IV Breast Cancer and the differences between them:-
Living With Stage : The Breast Cancer No One Understands
Editor’s note: We’re bringing back this piece from October 2014 for Metastatic Breast Cancer Awareness Day and to honor Jody Schoger, featured in the story. Schoger died of metastatic breast cancer in May. Want to learn more about MBC? Look for our tweets at the Northwest Metastatic Breast Cancer Conference this Saturday at Fred Hutch.
A no-nonsense Texan of 60 years, Jody Schoger* has a very no-nonsense way of educating people about her metastatic breast cancer.
âSomeone will say, âWhen are you done with treatment?â and Iâll tell them, âWhen Iâm dead,ââ said Schoger, a writer and cancer advocate who lives near Houston. âSo many people interpret survivorship as going across the board. That everybody survives cancer now. But everybody does not survive cancer.â
An estimated 155,000-plus women in the U.S. currently live with âmets,â or metastatic breast cancer. This type of cancer, also called stage 4 breast cancer, means the cancer has metastasized, or traveled, through the bloodstream to create tumors in the liver, lungs, brain, bones and/or other parts of the body. Between 20 and 30 percent of women with early stage breast cancer go on to develop metastatic disease. While treatable, metastatic breast cancer cannot be cured. The five-year survival rate for stage 4 breast cancer is 22 percent median survival is three years. Annually, the disease takes 40,000 lives.
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More Aggressive Breast Cancers Are Often Her
Breast cancer tumors with a positive HER-2 status are usually fast-growing and aggressive. There tends to be a higher level of HER-2 expression in higher-grade tumors than in lower grade tumors.
HER-2 receptors and also epidermal growth factor receptors are stimulants to cancer cell growth. Other hormonal factors of a tumor can also make cancer more aggressive.
Some breast cancer tumors will have a decrease in the level of tumor-suppressor genes, such as p53, which make invasion beyond the breast ducts more likely. A decrease in the levels of metastasis-suppressor genes such as nm23 also make spread to the lymph nodes and other areas of the body more likely.
HER-2 positive breast cancers do appear to be more likely to spread early in the cancer course to major visceral sites such as the:-
- axillary lymph nodes
- adrenal glands
What Research Is The Latest Research On Breast Cancer Is It Worthwhile To Participate In A Breast Cancer Clinical Trial
Without research and clinical trials, there would be no progress in our treatment of cancers.
Research can take many forms, including research in the laboratory directly on cancer cells or using animals. Research can also be performed using patient volunteers.
Research that a patient can be involved in is referred to as a clinical trial. In clinical trials, different treatment regimens are compared for side effects and outcomes, including long-term survival. Clinical trials aim to find out whether new approaches are safe and effective.
Whether one should participate in a clinical trial is a personal decision and should be based upon a full understanding of the advantages and disadvantages of the trial. One should discuss the trial with a health care team and ask how this trial might be different from the treatment one would usually receive.
Someone should never be forced to participate in a clinical trial or be involved in a trial without full understanding of the trial and a written and signed consent.
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A Note From Dr Halls Regarding The Statistics For Metastatic Recurrence In Breast Cancer
The statistic of 20% to 30% for metastatic breast cancer that recurs remain controversial amongst medical experts. The figure of 30% metastatic breast cancer recurrence rate first appears in a 2005medical study, but no statistical data or sources are cited.
The MBCN take the 18-year relative survival rate from the SEERS data between the years of 1990 to 1994 as 71%. The argument is, that this takes us close to the 30% recurrence rate statistic. However, there are many other factors at play and treatment has advanced so much that recurrence rates may have even halved since then.
It is safe to say that much more data and research into metastatic recurrence rates would be of huge value towards a long-term cancer cure.
Indeed, it has also been suggested that research into the rare group of women who survive many years with metastasis may be of equal importance to understanding recurrence and patterns of breast cancer.