Preferred Combination Chemotherapy With Trastuzumab
Regimens are as follows:
PCH: Carboplatin AUC 6 IV on day 1 plus paclitaxel 175 mg/m2 IV on day 1 every 3 wk plus trastuzumab or
Weekly PCH: Paclitaxel 80 mg/m2 IV on days 1, 8, and 15 plus carboplatin AUC 2 IV on days 1,8, and 15 every 4 wk plus trastuzumab
Pertuzumab/trastuzumab/docetaxel: pertuzumab 840 mg IV plus trastuzumab 8 mg/kg IV plus docetaxel 75 mg/m2 IV on day 1, then pertuzumab 420 mg plus trastuzumab 6 mg/kg plus docetaxel 75 mg/m2 q3 wk
- As an alternative, IV trastuzumab and IV pertuzumab may be substituted with Phesgo administer loading dose of 1,200 mg pertuzumab/600 mg trastuzumab SC x 1 dose followed by 600 mg pertuzumab/600 mg trastuzumab SC q3Weeks continue until disease recurrence or unmanageable toxicity, whichever occurs first
- Patients who received IV pertuzumab and trastuzumab within 6 weeks since their last dose should skip the loading dose and administer the maintenance dose of 600 mg pertuzumab/600 mg trastuzumab and every 3 weeks for subsequent administrations
Patient Selection/indications For Treatment
Multiple components determine the necessity for patients requiring adjuvant chemotherapy. These include but are not limited to the tumor size, molecular subtype, histology and its grade. The axillary and regional lymph node status and the tumor hormone receptor expression are also important considerations. Finally, the patients age, concomitant co-morbidities and their performance status play a significant role in determining the benefit of adjuvant chemotherapy. Other histologies require more information regarding size and nodal status to delineate the role of chemotherapy. Tumor size in the setting of regional disease is an independent prognostic factor with five-year overall survival for tumors 2 cm, 2.1 to 5 cm and 5 cm being 95, 82 and 63 percent, respectively. Nodal status also plays a role with any nodal involvement lowering the survival rate at five years.
Why Are Chemotherapies Divided Into Different Classes
Chemotherapies are divided into different classes based on how they affect the DNA in our cells. Disruption or harming the DNA of cancer cells causes them to die and prevents them from growing.
In many cases, a combination of two or more chemotherapy medications or a chemotherapy regimen will be used. A combination of medications is usually recommended to treat breast cancer because they affect DNA differently. A combination can attack breast cancer in different ways, raising the chance for a successful treatment.
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When Will I Start Chemotherapy And Targeted Therapy
In general, chemotherapy and HER2-targeted therapies are more likely to be given prior to surgery. Youll receive these treatments in cycles, with each period of treatment followed by a period of rest to let your body recover.
Chemotherapy begins on the first day of the cycle. Cycles can last anywhere from about two to four weeks, depending on the combination of drugs.
Chemotherapy generally lasts about three to six months. The total length of chemotherapy treatment may vary depending on the stage of breast cancer and a number of other factors.
Herceptin is usually given every three weeks for one year , initially in combination with chemotherapy and then on its own after chemotherapy is complete.
Expert Review And References
- Bursein HJ, Harris JR, Morrow M. Malignant tumors of the breast. Devita, V. T., Jr., Lawrence, T. S., & Rosenberg, S. A. Cancer: Principles & Practice of Oncology. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins 2008: 43.2: pp. 1606-54.
- Foxson SB, Lattimer JG & Felder B. Breast cancer. Yarbro, CH, Wujcki D, & Holmes Gobel B. . Cancer Nursing: Principles and Practice. 7th ed. Sudbury, MA: Jones and Bartlett 2011: 48: pp. 1091-1145.
- National Cancer Institute. Breast Cancer Treatment Health Professional Version. Bethesda, MD: National Cancer Institute 2010.
- Breast cancer. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. National Comprehensive Cancer Network 2010.
- 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.
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Feeling Unwell Or Tired
Many women do not feel as healthy after chemo as they did before. There is often a residual feeling of body pain or achiness and a mild loss of physical functioning. These changes may be very subtle and happen slowly over time.
Fatigue is another common problem for women who have received chemo. This may last a few months up to several years. It can often be helped, so its important to let your doctor or nurse know about it. Exercise, naps, and conserving energy may be recommended. If you have sleep problems, they can be treated. Sometimes fatigue can be a sign of depression, which may be helped by counseling and/or medicines.
Chemotherapy For Metastatic Breast Cancer
Advances in treatment are making it possible for women with metastatic breast cancer to live for many years. New drug therapies can not only slow down or stop a tumors growth but also keep symptoms at bay.
Which treatment your doctor recommends will vary based on your medical history, age, and breast cancer type, among other factors. Combinations of drugs are commonly prescribed for women with early-stage disease. Most women with advanced breast cancer generally receive only one drug at a time.
Chemotherapy drugs that MSK doctors commonly prescribe for advanced breast cancer include:
Women with advanced disease can also benefit from genomic testing. This is also called tumor sequencing or molecular profiling. It is offered to all MSK patients with metastatic breast cancer. Genomic testing involves looking at the cancer cells to see if there are any genetic mutations that could be linked to the specific type of breast cancer you have.
Our experts use a highly sophisticated testing approach developed by MSK researchers called MSK-IMPACT. The information gained from MSK-IMPACT can help us personalize your care. We can rule out drug therapies that may not work for you or sometimes recommend cutting-edge clinical trials designed to target the specific mutations in your tumor.
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When Might Chemotherapy Be Used For Breast Cancer
Chemotherapy may be able to cure breast cancer. This means the tumor disappears and doesnt grow back. If a cure isnt possible, chemotherapy may help keep the cancer from growing or spreading. If the cancer is advanced and cant be controlled, chemotherapy may help ease symptoms caused by cancer and improve your quality of life. A healthcare provider with special training in cancer treatment will talk to you about the goals of chemotherapy and the best treatment plan for you.
Your oncologist may advise chemotherapy in any of these situations:
Before surgery. This is called neoadjuvant chemotherapy. Chemotherapy may be used to shrink the tumor so that it’s smaller. This may allow you to have surgery to remove just part of the breast , instead of the entire breast .
After surgery. This is called adjuvant chemotherapy. Adjuvant chemotherapy helps keep any cancer cells that are left from growing and spreading. Whether your oncologist advises it depends on the size of the tumor, if it has spread to lymph nodes, and other factors. Chemotherapy is often given after surgery to remove breast cancer. It may be given every 2 or 3 weeks.
When the breast cancer has spread to other parts of your body. Chemotherapy travels around the body to kill cancer cells. So it can be used to kill cancer cells that have spread. How long this treatment lasts depends on how much the tumors shrink.
Treatment Recommendations For Inoperable Noninflammatory Locally Advanced Disease
Treatment includes chemotherapy, with or without a taxane. Regimens are as follows:
TAC: Docetaxel 75 mg/m2 IV on day 1 plus doxorubicin 50 mg/m2 IV on day 1 plus cyclophosphamide 500 mg/m2 IV on day 1 every 3 wk for six cycles or
Dose-dense AC-P: Doxorubicin 60 mg/m2 IV plus cyclophosphamide 600 mg/m2 every 2wk for four cycles, followed by paclitaxel 175 mg/m2 every 2 wk with colony-stimulating factor support or
AC: Doxorubicin 60 mg/m2 IV plus cyclophosphamide 600 mg/m2 IV on day 1 every 3 wk for four cycles or
TC: Docetaxel 75 mg/m2 IV on day 1 plus cyclophosphamide 600 mg/m2 IV on day 1 every 3 wk for four cycles
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Early Stage Her2 Positive Tumors
It has been hypothesized that a specific population of patients who may benefit from the use of anthracycline is that of patients with HER2 positive tumors. The National Surgical – Breast and Bowel Project 31 trial included women with HER2 positive, node positive breast cancer. Patients were assigned to treatment with doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab therapy. In conjunction with this trial was the North Central Cancer Treatment Group intergroup trial N9831 which enrolled women with HER2 positive node positive or high-risk node negative breast cancer. The women were treated with AC and T followed by no treatment, AC and T followed by sequential H or AC followed by concurrent T and H. From these two trials at a median follow up of 3.9 years, chemotherapy plus adjuvant trastuzumab compared to treatment without trastuzumab resulted in significantly superior DFS and OS .
Who Needs Breast Cancer Chemotherapy
Chemotherapy is offered to most patients based on several factors including:
- Type of receptors and status
- Number of lymph nodes involved and degree of involvement
- The risk for cancer to spread elsewhere in the body
Your medical team will work to select the right blend of chemotherapy drugs to suppress each stage of the cancer cells growth.
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The Birth Of Chemotherapy
After the Second World War, the observation by Goodman and Gilman that nitrogen mustards had the potential for anticancer effects , and parallel work on antifolates by , led to the first successful drug treatments for cancer . Subsequently, observations of uracil uptake by normal rat mucosa and tumours led to the development of 5-fluorouracil , and then cyclophosphamide+methotrexate+5-fluorouracil the first effective chemotherapy regimen for breast cancer .
CMF was tested in the 1970s by
Ipsilateral Breast Chest Wall Or Locoregional Recurrence
See the list below:
Patients with localized recurrence should undergo a thorough evaluation for metastatic disease, including a careful history and physical examination, bone scan, and computed tomography of the chest and abdomen clinically unsuspected metastases are not uncommon the tumor should be resected with an attempt to establish adequate tumor-free margins, whenever feasible
RT should also be administered to the chest wall and regional lymphatics, although this may be problematic for those who have previously undergone chest wall irradiation in the adjuvant setting
Systemic therapy should also be considered in order to decrease the likelihood of subsequent recurrence
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Longer Term Side Effects
Tiredness is commonly reported during treatment. This may be a direct effect of the drugs or may be due to other factors such as disrupted sleep patterns.
- Try to get adequate rest but also try to exercise regularly. Go for a walk outside each day as this can actually give you more energy.
- Find something that you actually enjoy doing and also try to incorporate exercise into your usual day, e.g. walk upstairs rather than taking the lift, park further away from where you want to go and walk the extra distance. Build this up gradually.
- Your GP, practice nurse or a physiotherapist can work with you to devise a specific exercise plan for you.
- Let others help when your energy levels are low.
If your fatigue doesn’t allow you to exercise, discuss this with your GP.
Usually energy levels recover after treatment finishes but this commonly takes time. In some cases full recovery may take 12 months or more.
Some people notice they are having concentration and short-term memory problems following their chemotherapy. This is often referred to as chemo brain. The severity and duration of symptoms differ from person to person. For some people the symptoms are very mild and resolve soon after treatment stops, but others may find their daily life is noticeably affected for a much longer period, restricting their ability to return to work in their pre-treatment capacity.
How Is Chemotherapy Given
Chemo drugs for breast cancer are typically given into a vein , either as an injection over a few minutes or as an infusion over a longer period of time. This can be done in a doctors office, infusion center, or in a hospital setting.
Often, a slightly larger and sturdier IV is required in the vein system to administer chemo. These are known as central venous catheters , central venous access devices , or central lines. They are used to put medicines, blood products, nutrients, or fluids right into your blood. They can also be used to take out blood for testing.
There are many different kinds of CVCs. The most common types are the port and the PICC line. For breast cancer patients, the central line is typically placed on the side opposite of the underarm that had lymph nodes removed for the breast cancer surgery.
Chemo is given in cycles, followed by a rest period to give you time to recover from the effects of the drugs. Cycles are most often 2 or 3 weeks long. The schedule varies depending on the drugs used. For example, with some drugs, the chemo is given only on the first day of the cycle. With others, it is given for a few days in a row, or once a week. Then, at the end of the cycle, the chemo schedule repeats to start the next cycle.
Adjuvant and neoadjuvant chemo is often given for a total of 3 to 6 months, depending on the drugs used. The length of treatment for advanced breast cancer depends on how well it is working and what side effects you have.
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Working With Your Healthcare Provider
It’s important to know which medicines you’re taking. Write your medicines down, ask your healthcare team how they work, and what side effects they might have.
Talk with your healthcare providers about what signs to look for and when to call them. Make sure you know what number to call with questions, even on evenings and weekends.
It may be helpful to keep a diary of your side effects. Write down physical, thinking, and emotional changes. A written list will make it easier for you to remember your questions when you go to your appointments. It will also make it easier for you to work with your healthcare team to make a plan to manage your side effects.
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Changing Chemotherapy Doses And Schedules
In most cases, the most effective doses and schedules of drugs to treat specific cancers have been found by testing them in clinical trials. Its important, when possible, to get the full course of chemo, the full dose, and keep the cycles on schedule. This gives a person the best chance of getting the maximum benefit from treatment.
There may be times, though, when serious side effects require adjusting the chemo plan to allow you time to recover. Sometimes, you might be given supportive medicines to help your body recover more quickly. Again, the key is to give enough chemo to kill the cancer cells without causing other serious problems.
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Preferred Agents For Trastuzumab
Regimens are as follows:
Capecitabine 1000 mg/m2 PO BID on days 1-14 plus lapatinib 1250 mg PO on days 1-21 every 3 wk or
Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus other first-line agents or
Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus capecitabine 2500 mg/m² on days 1-14 every 3 wk or
Trastuzumab 4 mg/kg IV on day 1 followed by 2 mg/kg IV weekly or 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus lapatinib 1000 mg PO daily or
Ado-trastuzumab: 3.6 mg/kg IV infusion q3 wk as a single agent in patients who previously received trastuzumab and a taxane, either separately or in combination
Trastuzumab deruxtecan: 5.4 mg/kg IV q3 wk as a single agent for unresectable or metastatic HER2-positive breast cancer in adults who have received 2 or more prior anti-HER2-based regimens in the metastatic setting
Trastuzumab 8 mg/kg IV on day 1 followed by 6 mg/kg every 3 wk plus capecitabine 1000 mg/m2 on days 1-14 every 3 wk plus tucatinib 300 mg PO BID
For patients with HER2/neu-negative disease, options include the following:
- Single-agent cytotoxic therapy
- Single-agent cytotoxic therapy plus bevacizumab
- Combination cytotoxic therapy
- Endocrine-based therapy
- Ribociclib , 600 mg/day PO for days 1-21 of a 28-day cycle, plus
- Fulvestrant 500 mg IM on days 1, 15, 29, and once monthly thereafter
Targeted Therapy For Her2
In about 1 in 5 women with breast cancer, the cancer cells have too much of a growth-promoting protein known as HER2 on their surface. These cancers, known as HER2-positive breastcancers, tend to grow and spread more aggressively. Different types of drugs have been developed that target the HER2 protein.
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