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Triple Positive Breast Cancer 2021

What Is Stage 0

Triple Negative Breast Cancer Case Panel Discussion | 2022 Best of Breast Conference

Stage 0 is the least invasive stage of breast cancer and usually detected early in patients, according to the American Cancer Society. In this stage, cancer cells or non-cancerous abnormal cells are only in the part of the breast in which they formed and havenât spread.

âAt this stage of breast cancer, we tell patients not to be too worried. Stage 0 is extremely treatable and we ask people not to shed a tear over the diagnosis just yet,â said Cruz.

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Understanding Her2+ Status And Survival

Doctors use three markers to help define breast cancers and guide treatment. One of those is the HER2 protein. The other two are hormone receptors . When a cancer has none of these, doctors call it triple negative. Until recently, there wasnt much information about how these markers changed survival rates for breast cancer.

A recent study looked at the National Cancer Institute data to see if there were differences in survival for women based on these markers. The study shows there are. Overall, women who have HR+ and HER2- breast cancer do best. But in the later stages, those who have the HER2+ type have better survival rates than those with HER2-. Breast cancers that are triple negative have the lowest survival rates. The 4-year survival rates are as follows:

  • HR+/HER2-: 92.5%

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What Is The Survival Rate Of Triple

According to the American Cancer Society, the 5-year survival rate for localized breast cancer is 99%. For breast cancer with regional spread the survival rate is 86%, and for breast cancer with metastasis is 28%. The overall survival rate for all stages is 90%. This means breast cancer patients are 90% as likely as healthy people to live for at least 5 years after their diagnosis of breast cancer.

In general, the behavior and survival rate for triple-positive breast tumors is similar to ER-positive/HER2-negative tumors. One study in California that looked at nearly 125,000 women with breast cancer found no major difference in survival rates between these types of tumors. Triple-negative tumors, in general, have a shorter survival rate compared to triple positive tumors. With that said, each patient and their cancer is unique. As noted, crosstalk between estrogen receptors and HER2 can lead to treatment resistance to hormonal therapies and HER2-directed treatments, reducing the survival rate.

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Pmrt After Neoadjuvant Systemic Therapy

Long-term results of 10 randomized trials confirm the equivalence of preoperative and postoperative chemotherapy in terms of breast cancer-specific survival and overall survival . Current guidelines state that radiation therapy is based on the maximum disease stage at diagnosis .

It is unknown if stage III complete responders could be spared of adjuvant radiation therapy, as well as if stage I/II non-responders, instead, should not . Retrospective studies have suggested that patients with residual HER-2-positive and TNBC are sensitive to radiation therapy to optimize locoregional control . Stage IIIII patients, especially with the triple negative subtype, also benefit from internal mammary nodal irradiation, according to a propensity-score matching retrospective study .

In conclusion, patients with TNBC are candidates for preoperative chemotherapy . Following BCS, all patients should be offered adjuvant radiation therapy . Prescription of radiation therapy is based on the maximum disease stage at diagnosis . It is unknown if patients with stage I/II TNBC and complete pathological response may forego adjuvant radiation therapy.

Recent Advances In Early Tnbc

Triple Negative Breast Cancer Drug Development Summit

The risk of relapse from TNBC has decreased with improved overall treatment and better chemotherapy regimens , even in the pre-immunotherapy and capecitabine era. In a British Columbia registry, the risk of relapse from TNBC decreased by 2540% between 19861992 and 20042008. Chemotherapy advances, which improved outcomes among all BC patients, particularly improved outcomes in TNBC. This includes the sequential addition of taxanes and the introduction of dose-dense schedules. The possibility to de-escalate to less toxic regimens omitting the anthracycline component in TNBC is still controversial. A benefit in 4-year invasive DFS of an anthracycline/taxane regimen versus taxane plus cyclophosphamide was seen in the approximately 1300-patient TNBC subset of the phase III ABC trials. Counter to this, the small 100-patient NeoSTOP trial randomized patients to an anthracycline/taxane regimen versus taxane plus carboplatin, finding similar pCR rates, and a meta-analysis based on the PlanB/SUCCESS-C trials, which included a similar subset of TNBC patients as in the ABC trials, compared AC-T to six cycles of TC finding, no difference in five-year DFS,,.

Fig. 3: Current multidisciplinary treatment of TNBC, including neoadjuvant chemotherapy plus immunotherapy, surgery and radiation, and adjuvant treatment with ongoing immunotherapy.

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Are We Close To A Cure

Every cancer is different, so finding a one-size-fits-all cure is unlikely anytime soon.

Research is targeting various methods, including gene editing, that have potential benefit for future treatments. Research is ongoing and new therapies are continually tested.

While living with metastatic breast cancer, there are ways to help improve your physical, emotional, and financial well-being.

In 2018, the released guidelines for improving the quality of life for people undergoing treatment.

The guidelines suggest the following steps:

  • Talk with your healthcare professional about managing pain and side effects from your treatment, such as nausea or fatigue, as well as other potential issues, like sexual health and fertility.
  • If youre experiencing depression or anxiety, check to see if a therapist or counselor is available at your cancer center, or join a breast cancer support group. Your healthcare team may have recommendations.
  • For help covering the cost of your treatment, talk with a financial counselor about assistance programs.

Frequency Of Low Her2 Expression

As of 11/15/2020, 1,973 patients were included in the AGMT-MBC-Registry . Out of 1,729 evaluable patients, who were diagnosed with MBC between November 2000 and August 2020, 351 were HER2-positive, 608 were HER2-low and 770 were completely HER2-negative . In 459 patients , the receptor status was determined in metastatic tissue and in 1270 patients in the primary tumor. Low HER2-expression was markedly more frequent in the HR+ subgroup compared to the HR- subgroup . The frequencies of all three HER2 subgroups in dependency of the HR status are shown in Fig. . When HER2patients were excluded, 44% of all HER2-negative patients, 48% of patients with HR+ /HER2- tumors and 33% of patients with triple-negative tumors showed a low-level expression of HER2, respectively.

Fig. 1

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Questions To Ask Your Doctor About Her2

  • What are my treatment options?
  • What is the best course of treatment for my cancer, and why?
  • Whats the overall goal of treatment in my case?
  • When should I start treatment?
  • Can I still work and manage my regular activities during this time?
  • How often will I be coming in to see you for treatment?
  • Will I be coming here for all my visits and treatments, or going elsewhere?
  • What short-term side effects and long-term risks are associated with my treatment?
  • What are the next steps if the desired treatment doesnt work?
  • How likely is it for my cancer to come back in the future? What symptoms should I be aware of?
  • What is the cost of my treatment?
  • What should I discuss with my insurance company?

Have You Noticed Any Lumps In Your Breasts

Triple Negative Breast Cancer: What You Need to Know

A few weeks earlier, during Salvadors yearly well-woman checkup, her OB-GYN asked: Anna, have you noticed any lumps on your left breast?

At the time, Salvador didnt think twice about it. She was pursuing her masters degree in organizational development. One of her daughters was about to graduate from the University of Colorado Boulder with a bachelors and masters degree in psychology and linguistics. Another was enrolled in environmental sciences at Stanford. Salvador had also interviewed for a promotion at USAA, where she has worked for 20 years.

Nonetheless, her OB-GYN ordered a diagnostic mammogram after the well-woman checkup in November 2020. Salvador let her boss know shed be away from her desk for a few hours and she would be right back to work. No big deal.

The diagnostic mammogram went well, but the nearly three-hour wait afterward was agonizing. Then came the news from a doctor: I am so sorry to say, this is breast cancer.

Salvador wept and shook uncontrollably. The doctor said she would need a biopsy and referred her to UCHealths Dr. Pomerenke. Salvador, a devout Catholic who worships the Virgin Mary, relied on her faith.

When I got the biopsy, I was praying the rosary. Please, please dont test positive for the cancer.

Tests showed Salvador had three types of cancer: HER2, estrogen and progesterone. Pomerenke relayed the results directly, but compassionately. The only thing Salvador could say was: Oh my God oh my God.

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Clinicopathological Characteristics Of Patients

Among 491,913 patients originally identified from SEER database, cases of 33,339 TP-FBCs and 336 TP-MBCs from 2010 to 2017 were included in our study. According to the percentage of TP-FBC/TP-MBC to total FBC/MBC at each year , we firstly showed the trends of the subsets in 8 years . Generally, the subtype of TPBC was more prevalent in males than that in females with the exception of 2012.

Fig. 1

Clinical pathological characteristics of TP-MBC compared with TP-FBC were summarized in Table . TP-MBC patients are significantly older than TP-FBC , patients older than 65years account for almost half in TP-MBC. TP-MBC had less Asian/pacific islanders , more ductal carcinoma , higher clinical stage as well as T stage , N stage , M stage . However, there was no significant difference in tumor grade and surgery status between TP-MBC and TP-FBC.

Table 1 Clinical pathological characteristics of TP-MBC compared with TP-FBC

In Table , data of distant organ metastasis in TP-MBC and TP-FBC was shown. Compared with TP-FBC, TP-MBC patients had higher proportions of bone metastasis and lung metastasis . Significant difference was not found in the brain metastasis or liver metastasis between TP-MBC and TP-FBC.

Table 2 Comparison of distant organ metastasis patterns in TP-MBC and TP-FBC

Cancer And The Female Breast

Figure: Breast and Adjacent Lymph Nodes

Figure: The female breast along with lymph nodes and vessels. An inset shows a close-up view of the breast with the following parts labeled: lobules, lobe, ducts, nipple, areola, and fat.

Inside a woman’s breast are 15 to 20 sections, or lobes. Each lobe is made of many smaller sections called lobules. Fibrous tissue and fat fill the spaces between the lobules and ducts . Breast cancer occurs when cells in the breast grow out of control and form a growth or tumor. Tumors may be cancerous or not cancerous .

Additional Information

Kohler BA, Sherman RL, Howlader N, Jemal A, Ryerson AB, Henry KA, Boscoe FP, Cronin KA, Lake A, Noone AM, Henley SJ, Eheman CR, Anderson RN, Penberthy L. Annual Report to the Nation on the Status of Cancer, 1975-2011, Featuring Incidence of Breast Cancer Subtypes by Race/Ethnicity, Poverty, and State. J Natl Cancer Inst. 2015 Mar 30 107:djv048. doi: 10.1093/jnci/djv048. Print 2015 Jun.

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What Research Trials Are Underway

There are several new and ongoing studies looking at treatments for triple-negative breast cancer.

Dr. Fancher encouraged people with triple-negative breast cancer to look into trials. Research on clinical trials is really important, she told MNT.

If you triple-negative breast cancer, consider a clinical trial. It helps move the research forward. There are lots of trials out there, and many are having good results.

Dr. Nan spoke about the Keynote 522 clinical trial . This trial is looking at the use of pembrolizumab, a type of immunotherapy, in combination with chemotherapy before and after surgery.

The trial focuses on people with stage 2 or 3 breast cancer who are at high risk, and pembrolizumab has shown some promise. In fact, the trial has shown a 65% effectiveness rate, indicating no residual signs of cancer in the tissue. This is up from 51% previously.

The phase 3 ASCENT clinical trial is looking at the use of sacituzumab govitecan, an antibody drug conjugate. In a phase 2 trial, it had shown promise in people who had previously received treatment for metastatic triple-negative breast cancer. The Food and Drug Administration gave the drug accelerated approval in 2020.

A person should talk with a doctor before joining a clinical trial. They may be able to help the person find a relevant study or recommend ones that will work best for them.

Study: New Genes Linked With Triple Negative Breast Cancer

Positive Strides in Triple

A research study identified new genes that may be associated with a higher risk for triple negative breast cancer.

This image is an example of the kind of gel pictures researchers use to understand the order, or sequence, of genes or to look for mutations in genes.

This image is an example of the kind of gel pictures researchers use to understand the order, or sequence, of genes or to look for mutations in genes.

Out of 100 people with breast cancer about 15 will have triple-negative breast cancer . Its one of the most challenging types of breast cancer to treat due to several things:

  • TNBC tends to be more aggressive than other common types of breast cancer.
  • Women usually dont learn they have it until the cancer has already spread to other parts of the body .
  • Treatment options remain limited.Hormone therapies and targeted therapies that help treat people with some types of breast cancer, typically dont work for a woman with TNBC. Doctors use chemotherapy to treat these patients, but it isnt very effective and may have side effects.

If doctors had a way to identify women at risk for TNBC, they might be able to find cancer earlier and before it spreads when it might be easier to treat. And, if doctors had a way to personalize treatment for women with TNBC, they might be able to improve a womans outlook . One approach researchers are using to identify women at risk for TNBC and possible treatment options for TNBC is by studying inherited changes in cancer genes.

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Research Agenda For The Next Decade

The introduction of immunotherapy marks a revolution in the treatment of early-stage TNBC. KEYNOTE-522 has shown that, by unleashing anti-cancer immune responses through ICIs, long-term benefits can be obtained for the treatment of this aggressive BC subtype. However, it represents a starting point rather than a finish line, and additional efforts will be required precisely implement immunotherapy for the treatment of TNBC .

Fig. 1: Next decade research agenda for neo immunotherapy in TNBC.

Abbreviations: IO, immunotherapy, TNBC, triple negative breast cancer TMB, tumor mutational burden ADC, antibody-drug conjugate ER, estrogen receptor CD, cluster of differentiation TILs, tumor infiltrating lymphocytes PD-L1, Programmed death-ligand 1 HLA, human leukocyte antigen PD-1, Programmed cell death protein 1 A, adenosine T, thymine C, cytosine G, guanine BRCA, BReast CAncer gene EFS, event-freee survival RD, residual disease me1, mono-methylated form BC, breast cancer. Created with biorender.com.

How Do Breast Cancer Cells Spread Around The Body

Breast cancer cells travel through the body like any other cancer cells. Firstly, cancer cells can invade neighbouring healthy tissue. Following this, the cancer cells then invade local lymph nodes or blood vessels.

When breast cancer spreads to the axillary lymph nodes this is still a relatively early stage of metastasis, and potentially curable.

The cancer cells will typically travel through the lymphatic system or blood vessels to other distant parts of the body.

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Detecting Breast Cancer With Screening And Awareness

One of the best ways to improve your chances of surviving breast cancer is to be vigilant about getting routine screenings for the disease. The earlier cancer is found, the better the outlook. According to the ACS, screening reduces breast cancer deaths by 20%. The ACS says that women at average risk for breast cancer should have the option of starting annual screening mammograms between ages 40 to 44 years, while women ages 45 to 54 years should have annual mammograms. Starting at age 55, women should have the option of receiving a mammogram every year or every two years, the ACS says.

Dr. Cairoli points out that younger women who arent covered by screening recommendations should not assume theyre not susceptible to breast cancer. Unfortunately, theres no such thing as too young. Breast cancers can occur in patients even in their 20s. He recommends that all women, especially those not yet of screening age, perform monthly breast self-examinations.Monthly breast self-exams havent been shown to improve outcomes for the population at large, but by knowing your body youll be able to alert your physician if you notice a change, Dr. Cairoli says. And if you do find something unusual, he adds, insist on a physical examination or screening even if your doctor tries to tell you youre too young for breast cancer.

Breast cancer symptoms to be alert for include:


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Her2 Immunohistochemical Staining And Her2 Fish Results Before Neoadjuvant Chemotherapy

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Fifty-two tumors showed 3+ staining, 28 showed 2+staining, and 5 showed 0/1+staining . FISH was performed in 36 cases including 4 cases that showed 3+ HER2 IHC staining. The mean FISH HER2/CEP17 ratio for all tumors studied was 3.6 and the mean HER2 signals per cell was 8 . Sixteen tumors showed low amplification defined as HER2/CEP17 ratio of 2 or greater and 4 to 6 HER2 signals per cell,14 which included 14 tumors with 2+ staining and 2 with 0/1+ staining. No tumors showed other nonclassical FISH results such as monosomy-like or coamplification/polysomy.15

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