Does Herceptin (trastuzumab) cause side effects?
Herceptin (trastuzumab) is a monoclonal antibody that is part of a chemotherapy regimen that is used to prevent recurrence of breast cancer, and for the treatment of breast cancer that has spread beyond the breast (metastasized).
A cancer cell has various receptors on its surface. Chemicals bind to these receptors and cause changes within the cancer cell. One of the receptors that occurs in about one-third of all breast cancers is called HER2.
HER2 is known to control the growth and development of the cancer cells, and the production of new cancer cells. If HER2 receptors are present in large numbers on the cancer cells (often referred to as overexpression of HER2), then the cancer cells may multiply and grow quickly.
Normally, the immune system produces antibodies that will detect and attack HER2 receptors to slow the growth of cancer cells; however, if HER2 is present in large numbers, the immune system may be unable to control HER2. Herceptin is thought to block the HER2 receptors when there is overexpression, thereby blocking growth of the cancer.
Common side effects of Herceptin include
- prickling or burning sensation in the skin,
- upper respiratory or a catheter-related infection,
- increased cough,
- nausea and vomiting,
- infusion-related reactions including mild to moderate chills and/or fever,
- weight loss,
- inflammation of the mouth and lips,
- shortness of breath,
- distortion of taste,
- cough, and
Other side effects of Herceptin include
Serious side effects of Herceptin include
- heart failure,
- pulmonary toxicity,
- serious allergic reactions,
- fetal toxicity,
- decreased red and/or white blood cells,
- herpes simplex infections,
- urinary tract infections (UTIs),
- sepsis, and
Drug interactions of Herceptin include paclitaxel, which may increase blood levels of Herceptin.
What are the important side effects of Herceptin (trastuzumab)?
- Trastuzumab can cause heart failure, especially when it is combined with cyclophosphamide and anthracycline-containing chemotherapy regimens. Left ventricular function should be monitored prior to and during treatment.
- It should be stopped in patients receiving adjuvant therapy, and withheld in patients with metastatic cancer if the function of the heart decreases significantly.
Common side effects include:
- Diarrhea (25% of patients)
- A prickling or burning sensation in the skin (9% of patients)
- Either an upper respiratory or a catheter-related infection (26% of patients)
- Increased cough (26% of patients)
- Nausea and vomiting (23%-33% of patients)
- Rash (18% of patients)
- infusion-related side effects including mild to moderate chills and/or fever (40% of patients)
- Weight loss
- Shortness of breath
- Distortion of taste
Other side effects include:
Possible serious side effects include:
- Heart failure
- Pulmonary toxicity
- Serious allergic reactions
- Fetal toxicity
- Decreased red and/or white blood cells,
- Herpes simplex infections
- Urinary tract infections
Trastuzumab can cause serious and fatal infusion reactions and pulmonary toxicity. Symptoms usually occur during treatment or within 24 hours of treatment. The infusion should be interrupted if patients develop shortness of breath or significant reduction in blood pressure, and patients should be monitored until symptoms completely resolve.
Trastuzumab should be stopped if any of the following occurs:
Use of trastuzumab during pregnancy can cause oligohydramnios and oligohydramnios sequence, manifesting as pulmonary hypoplasia, skeletal abnormalities, and death of the baby.
Herceptin (trastuzumab) side effects list for healthcare professionals
The following adverse reactions are discussed in greater detail in other sections of the label:
- Infusion Reactions
- Embryo-Fetal Toxicity
- Pulmonary Toxicity
- Exacerbation of Chemotherapy-Induced Neutropenia
The most common adverse reactions in patients receiving Herceptin in the adjuvant and metastatic breast cancer setting are
- infusion reactions,
- increased cough,
- anemia, and
Adverse reactions requiring interruption or discontinuation of Herceptin treatment include
- significant decline in left ventricular cardiac function,
- severe infusion reactions, and
- pulmonary toxicity.
In the metastatic gastric cancer setting, the most common adverse reactions (≥ 10%) that were increased (≥ 5% difference) in the Herceptin arm as compared to the chemotherapy alone arm were
- weight loss,
- upper respiratory tract infections,
- mucosal inflammation,
- nasopharyngitis, and
The most common adverse reactions which resulted in discontinuation of treatment on the Herceptincontaining arm in the absence of disease progression were
- diarrhea, and
- febrile neutropenia.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adjuvant Breast Cancer Studies
The data below reflect exposure to one-year Herceptin therapy across three randomized, open-label studies, Studies 1, 2, and 3, with (n = 3678) or without (n = 3363) trastuzumab in the adjuvant treatment of breast cancer.
The data summarized in Table 3 below, from Study 3, reflect exposure to Herceptin in 1678 patients; the median treatment duration was 51 weeks and median number of infusions was 18. Among the 3386 patients enrolled in the observation and one-year Herceptin arms of Study 3 at a median duration of follow-up of 12.6 months in the Herceptin arm, the median age was 49 years (range: 21 to 80 years), 83% of patients were Caucasian, and 13% were Asian.
Table 3 : Adverse Reactions for Study 3a, All Gradesb
|Adverse Reaction||One Year Herceptin|
(n = 1678)
(n = 1708)
|Hypertension||64 (4%)||35 (2%)|
|Dizziness||60 (4%)||29 (2%)|
|Ejection Fraction Decreased||58 (3.5%)||11 (0.6%)|
|Palpitations||48 (3%)||12 (0.7%)|
|Cardiac Arrhythmiasc||40 (3%)||17 (1%)|
|Cardiac Failure Congestive||30 (2%)||5 (0.3%)|
|Cardiac Failure||9 (0.5%)||4 (0.2%)|
|Cardiac Disorder||5 (0.3%)||0 (0%)|
|Ventricular Dysfunction||4 (0.2%)||0 (0%)|
|Respiratory Thoracic Mediastinal Disorders|
|Cough||81 (5%)||34 (2%)|
|Influenza||70 (4%)||9 (0.5%)|
|Dyspnea||57 (3%)||26 (2%)|
|URI||46 (3%)||20 (1%)|
|Rhinitis||36 (2%)||6 (0.4%)|
|Pharyngolaryngeal Pain||32 (2%)||8 (0.5%)|
|Sinusitis||26 (2%)||5 (0.3%)|
|Epistaxis||25 (2%)||1 (0.06%)|
|Pulmonary Hypertension||4 (0.2%)||0 (0%)|
|Interstitial Pneumonitis||4 (0.2%)||0 (0%)|
|Diarrhea||123 (7%)||16 (1%)|
|Nausea||108 (6%)||19 (1%)|
|Vomiting||58 (3.5%)||10 (0.6%)|
|Constipation||33 (2%)||17 (1%)|
|Dyspepsia||30 (2%)||9 (0.5%)|
|Upper Abdominal Pain||29 (2%)||15 (1%)|
|Musculoskeletal & Connective Tissue Disorders|
|Arthralgia||137 (8%)||98 (6%)|
|Back Pain||91 (5%)||58 (3%)|
|Myalgia||63 (4%)||17 (1%)|
|Bone Pain||49 (3%)||26 (2%)|
|Muscle Spasm||46 (3%)||3 (0.2%)|
|Nervous System Disorders|
|Headache||162 (10%)||49 (3%)|
|Paraesthesia||29 (2%)||11 (0.6%)|
|Skin & Subcutaneous Tissue Disorders|
|Rash||70 (4%)||10 (0.6%)|
|Nail Disorders||43 (2%)||0 (0%)|
|Pruritus||40 (2%)||10 (0.6%)|
|Pyrexia||100 (6%)||6 (0.4%)|
|Edema Peripheral||79 (5%)||37 (2%)|
|Chills||85 (5%)||0 (0%)|
|Asthenia||75 (4.5%)||30 (2%)|
|Influenza-like Illness||40 (2%)||3 (0.2%)|
|Sudden Death||1 (0.06%)||0 (0%)|
|Nasopharyngitis||135 (8%)||43 (3%)|
|UTI||39 (3%)||13 (0.8%)|
|Immune System Disorders|
|Hypersensitivity||10 (0.6%)||1 (0.06%)|
|Autoimmune Thyroiditis||4 (0.3%)||0 (0%)|
|a Median follow-up duration of 12.6 months in the one-year Herceptin treatment arm.|
b The incidence of Grade 3 or higher adverse reactions was <1% in both arms for each listed term.
c Higher level grouping term.
- In Study 3, a comparison of 3-weekly Herceptin treatment for two years versus one year was also performed.
- The rate of asymptomatic cardiac dysfunction was increased in the 2-year Herceptin treatment arm (8.1% versus 4.6% in the one-year Herceptin treatment arm).
- More patients experienced at least one adverse reaction of Grade 3 or higher in the 2-year Herceptin treatment arm (20.4%) compared with the one-year Herceptin treatment arm (16.3%).
- The safety data from Studies 1 and 2 were obtained from 3655 patients, of whom 2000 received Herceptin; the median treatment duration was 51 weeks.
- The median age was 49 years (range: 24-80);
- 84% of patients were White,
- 7% Black,
- 4% Hispanic, and
- 3% Asian.
- In Study 1, only Grade 3-5 adverse events, treatment-related Grade 2 events, and Grade 2-5 dyspnea were collected during and for up to 3 months following protocol-specified treatment.
- The following non-cardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients receiving Herceptin plus chemotherapy as compared to chemotherapy alone:
- fatigue (29.5% vs. 22.4%),
- infection (24.0% vs. 12.8%),
- hot flashes (17.1% vs. 15.0%),
- anemia (12.3% vs. 6.7%),
- dyspnea (11.8% vs. 4.6%),
- rash/desquamation (10.9% vs. 7.6%),
- leukopenia (10.5% vs. 8.4%),
- neutropenia (6.4% vs. 4.3%),
- headache (6.2% vs. 3.8%),
- pain (5.5% vs. 3.0%),
- edema (4.7% vs. 2.7%), and
- insomnia (4.3% vs. 1.5%).
- The majority of these events were Grade 2 in severity.
- In Study 2, data collection was limited to the following investigator-attributed treatment-related adverse reactions:
- NCI-CTC Grade 4 and 5 hematologic toxicities,
- Grade 3-5 non-hematologic toxicities,
- selected Grade 2-5 toxicities associated with taxanes (myalgia, arthralgias, nail changes, motor neuropathy, and sensory neuropathy) and
- Grade 1-5 cardiac toxicities occurring during chemotherapy and/or Herceptin treatment.
- The following non-cardiac adverse reactions of Grade 2-5 occurred at an incidence of at least 2% greater among patients receiving Herceptin plus chemotherapy as compared to chemotherapy alone:
- arthralgia (12.2% vs. 9.1%),
- nail changes (11.5% vs. 6.8%),
- dyspnea (2.4% vs. 0.2%), and
- diarrhea (2.2% vs. 0%).
- The majority of these events were Grade 2 in severity.
- Safety data from Study 4 reflect exposure to Herceptin as part of an adjuvant treatment regimen from 2124 patients receiving at least one dose of study treatment [AC-TH: n = 1068; TCH: n=1056].
- The overall median treatment duration was 54 weeks in both the AC-TH and TCH arms.
- The median number of infusions was 26 in the AC-TH arm and 30 in the TCH arm, including weekly infusions during the chemotherapy phase and every three week dosing in the monotherapy period.
- Among these patients, the median age was 49 years (range 22 to 74 years).
- In Study 4, the toxicity profile was similar to that reported in Studies 1, 2, and 3 with the exception of a low incidence of CHF in the TCH arm.
Metastatic Breast Cancer Studies
- The data below reflect exposure to Herceptin in one randomized, open-label study, Study 5, of chemotherapy with (n = 235) or without (n = 234) trastuzumab in patients with metastatic breast cancer, and one single-arm study (Study 6; n = 222) in patients with metastatic breast cancer.
- Data in Table 4 are based on Studies 5 and 6.
- Among the 464 patients treated in Study 5, the median age was 52 years (range: 25-77 years).
- Eighty-nine percent were White,
- 5% Black,
- 1% Asian, and
- 5% other racial/ethnic groups.
- All patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly.
- The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 58% and 9%, respectively.
- Among the 352 patients treated in single agent studies (213 patients from Study 6), the median age was 50 years (range 28-86 years),
- 86% were White,
- 3% were Black,
- 3% were Asian, and
- 8% in other racial/ethnic groups.
- Most of the patients received 4 mg/kg initial dose of Herceptin followed by 2 mg/kg weekly.
- The percentages of patients who received Herceptin treatment for ≥ 6 months and ≥ 12 months were 31% and 16%, respectively.
Table 4 : Per-Patient Incidence of Adverse Reactions Occurring in ≥ 5% of Patients in Uncontrolled Studies or at Increased Incidence in the Herceptin Arm (Studies 5 and 6)
n = 352
|Herceptin + Paclitaxel|
n = 91
n = 95
|Herceptin + ACb|
n = 143
n = 135
|Body as a Whole|
|Congestive heart failure||7%||11%||1%||28%||7%|
|Nausea and vomiting||8%||14%||11%||18%||9%|
|Heme & Lymphatic|
|Urinary tract infection||5%||18%||14%||13%||7%|
|a Data for Herceptin single agent were from 4 studies, including 213 patients from Study 6.|
b Anthracycline (doxorubicin or epirubicin) and cyclophosphamide.
Metastatic Gastric Cancer
The data below are based on the exposure of 294 patients to Herceptin in combination with a fluoropyrimidine (capecitabine or 5-FU) and cisplatin (Study 7).
- In the Herceptin plus chemotherapy arm, the initial dose of Herceptin 8 mg/kg was administered on Day 1 (prior to chemotherapy) followed by 6 mg/kg every 21 days until disease progression.
- Cisplatin was administered at 80 mg/m² on Day 1 and the fluoropyrimidine was administered as either capecitabine 1000 mg/m² orally twice a day on Days 1-14 or 5-fluorouracil 800 mg/m²/day as a continuous intravenous infusion Days 1 through 5.
- Chemotherapy was administered for six 21-day cycles.
- Median duration of Herceptin treatment was 21 weeks; median number of Herceptin infusions administered was eight.
Table 5 : Study 7: Per Patient Incidence of Adverse Reactions of All Grades (Incidence ≥ 5% between Arms) or Grade 3/4 (Incidence > 1% between Arms) and Higher Incidence in Herceptin Arm
|Body System/Adverse Event||Herceptin + FC|
(N = 294) N (%)
(N = 290) N (%)
|All Grades||Grades 3/4||All Grades||Grades 3/4|
|Neutropenia||230 (78)||101 (34)||212 (73)||83 (29)|
|Hypokalemia||83 (28)||28 (10)||69 (24)||16 (6)|
|Anemia||81 (28)||36 (12)||61 (21)||30 (10)|
|Thrombocytopenia||47 (16)||14 (5)||33 (11)||8 (3)|
|Blood and Lymphatic System Disorders|
|Febrile Neutropenia||—||15 (5)||—||8 (3)|
|Diarrhea||109 (37)||27 (9)||80 (28)||11 (4)|
|Stomatitis||72 (24)||2 (1)||43 (15)||6 (2)|
|Dysphagia||19 (6)||7 (2)||10 (3)||1 (< 1)|
|Body as a Whole|
|Fatigue||102 (35)||12 (4)||82 (28)||7 (2)|
|Fever||54 (18)||3 (1)||36 (12)||0 (0)|
|Mucosal Inflammation||37 (13)||6 (2)||18 (6)||2 (1)|
|Chills||23 (8)||1 (< 1)||0 (0)||0 (0)|
|Metabolism and Nutrition Disorders|
|Weight Decrease||69 (23)||6 (2)||40 (14)||7 (2)|
|Infections and Infestations|
|Upper Respiratory Tract Infections||56 (19)||0 (0)||29 (10)||0 (0)|
|Nasopharyngitis||37 (13)||0 (0)||17 (6)||0 (0)|
|Renal and Urinary Disorders|
|Renal Failure and Impairment||53 (18)||8 (3)||42 (15)||5 (2)|
|Nervous System Disorders|
|Dysgeusia||28 (10)||0 (0)||14 (5)||0 (0)|
The following subsections provide additional detail regarding adverse reactions observed in clinical trials of adjuvant breast cancer, metastatic breast cancer, metastatic gastric cancer, or post-marketing experience.
- Serial measurement of cardiac function (LVEF) was obtained in clinical trials in the adjuvant treatment of breast cancer.
- In Study 3, the median duration of follow-up was 12.6 months (12.4 months in the observation arm; 12.6 months in the 1-year Herceptin arm); and in Studies 1 and 2, 7.9 years in the AC-T arm, 8.3 years in the AC-TH arm.
- In Studies 1 and 2, 6% of all randomized patients with post-AC LVEF evaluation were not permitted to initiate Herceptin following completion of AC chemotherapy due to cardiac dysfunction (LVEF < LLN or ≥ 16 point decline in LVEF from baseline to end of AC).
- Following initiation of Herceptin therapy, the incidence of new-onset dose-limiting myocardial dysfunction was higher among patients receiving Herceptin and paclitaxel as compared to those receiving paclitaxel alone in Studies 1 and 2, and in patients receiving one-year Herceptin monotherapy compared to observation in Study 3 (see Table 6, Figures 1 and 2).
- The per-patient incidence of new-onset cardiac dysfunction, as measured by LVEF, remained similar when compared to the analysis performed at a median follow-up of 2.0 years in the AC-TH arm.
- This analysis also showed evidence of reversibility of left ventricular dysfunction, with 64.5% of patients who experienced symptomatic CHF in the AC-TH group being asymptomatic at latest follow-up, and 90.3% having full or partial LVEF recovery.
Table 6a : Per-patient Incidence of New Onset Myocardial Dysfunction (by LVEF) Studies 1, 2, 3 and 4
|LVEF < 50% and Absolute Decrease from Baseline||Absolute LVEF Decrease|
|LVEF < 50%||≥ 10% decrease||≥ 16% decrease||< 20% and ≥ 10%||≥ 20%|
|Studies 1 & 2bc|
|(n = 1856)||(428)||(344)||(208)||(703)||(166)|
|(n = 1170)||(137)||(82)||(35)||(259)||(40)|
|(n = 1678)||(144)||(118)||(64)||(376)||(59)|
|(n = 1708)||(46)||(35)||(20)||(204)||(21)|
|(n = 1056)||(90)||(62)||(35)||(364)||(67)|
|(n = 1068)||(182)||(142)||(105)||(473)||(141)|
|(n = 1050)||(100)||(69)||(35)||(357)||(58)|
|a For Studies 1, 2 and 3, events are counted from the beginning of Herceptin treatment. For Study 4, events are counted from the date of randomization.|
b Studies 1 and 2 regimens: doxorubicin and cyclophosphamide followed by paclitaxel (AC→T) or paclitaxel plus Herceptin (AC→TH).
c Median duration of follow-up for Studies 1 and 2 combined was 8.3 years in the AC→TH arm.
d Median follow-up duration of 12.6 months in the one-year Herceptin treatment arm.
e Study 4 regimens: doxorubicin and cyclophosphamide followed by docetaxel (AC→T) or docetaxel plus Herceptin (AC→TH); docetaxel and carboplatin plus Herceptin (TCH).
Figure 1 : Studies 1 and 2: Cumulative Incidence of Time to First LVEF Decline of ≥ 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event
Time 0 is initiation of paclitaxel or Herceptin + paclitaxel therapy.
Figure 2 : Study 3: Cumulative Incidence of Time to First LVEF Decline of ≥ 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event
Time 0 is the date of randomization.
Figure 3 : Study 4: Cumulative Incidence of Time to First LVEF Decline of ≥ 10 Percentage Points from Baseline and to Below 50% with Death as a Competing Risk Event
Time 0 is the date of randomization.
The incidence of treatment emergent congestive heart failure among patients in the metastatic breast cancer trials was classified for severity using the New York Heart Association classification system (I-IV, where IV is the most severe level of cardiac failure) (see Table 2). In the metastatic breast cancer trials, the probability of cardiac dysfunction was highest in patients who received Herceptin concurrently with anthracyclines.
In Study 7, 5.0% of patients in the Herceptin plus chemotherapy arm compared to 1.1% of patients in the chemotherapy alone arm had LVEF value below 50% with a ≥10% absolute decrease in LVEF from pretreatment values.
- During the first infusion with Herceptin, the symptoms most commonly reported were chills and fever, occurring in approximately 40% of patients in clinical trials.
- Symptoms were treated with acetaminophen, diphenhydramine, and meperidine (with or without reduction in the rate of Herceptin infusion); permanent discontinuation of Herceptin for infusion reactions was required in < 1% of patients.
- Other signs and/or symptoms may include
- Infusion reactions occurred in 21% and 35% of patients, and were severe in 1.4% and 9% of patients, on second or subsequent Herceptin infusions administered as monotherapy or in combination with chemotherapy, respectively.
- In the post-marketing setting, severe infusion reactions, including hypersensitivity, anaphylaxis, and angioedema have been reported.
- In randomized controlled clinical trials, the overall incidence of anemia (30% vs. 21% [Study 5]), of selected NCI-CTC Grade 2-5 anemia (12.3% vs. 6.7% [Study 1]), and of anemia requiring transfusions (0.1% vs. 0 patients [Study 2]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone.
- Following the administration of Herceptin as a single agent (Study 6), the incidence of NCI-CTC Grade 3 anemia was < 1%. In Study 7 (metastatic gastric cancer), on the Herceptin containing arm as compared to the chemotherapy alone arm, the overall incidence of anemia was 28% compared to 21% and of NCICTC Grade 3/4 anemia was 12.2% compared to 10.3%.
- In randomized controlled clinical trials in the adjuvant setting, the incidence of selected NCI-CTC Grade 4-5 neutropenia (1.7% vs. 0.8% [Study 2]) and of selected Grade 2-5 neutropenia (6.4% vs. 4.3% [Study 1]) were increased in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone.
- In a randomized, controlled trial in patients with metastatic breast cancer, the incidences of NCI-CTC Grade 3/4 neutropenia (32% vs. 22%) and of febrile neutropenia (23% vs. 17%) were also increased in patients randomized to Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone.
- In Study 7 (metastatic gastric cancer) on the Herceptin containing arm as compared to the chemotherapy alone arm, the incidence of NCI-CTC Grade 3/4 neutropenia was 36.8% compared to 28.9%; febrile neutropenia 5.1% compared to 2.8%.
- The overall incidences of infection (46% vs. 30% [Study 5]), of selected NCI-CTC Grade 2-5 infection/febrile neutropenia (24.3% vs. 13.4% [Study 1]) and of selected Grade 3-5 infection/febrile neutropenia (2.9% vs. 1.4% [Study 2]) were higher in patients receiving Herceptin and chemotherapy compared with those receiving chemotherapy alone.
- The most common site of infections in the adjuvant setting involved the upper respiratory tract, skin, and urinary tract.
- In Study 4, the overall incidence of infection was higher with the addition of Herceptin to AC-T but not to TCH [44% (AC-TH), 37% (TCH), 38% (AC-T)]. The incidences of NCI-CTC Grade 3-4 infection were similar [25% (AC-TH), 21% (TCH), 23% (AC-T)] across the three arms.
- In a randomized, controlled trial in treatment of metastatic breast cancer, the reported incidence of febrile neutropenia was higher (23% vs. 17%) in patients receiving Herceptin in combination with myelosuppressive chemotherapy as compared to chemotherapy alone.
Adjuvant Breast Cancer
- Among women receiving adjuvant therapy for breast cancer, the incidence of selected NCI-CTC Grade 2-5 pulmonary toxicity (14.3% vs. 5.4% [Study 1]) and of selected NCI-CTC Grade 3-5 pulmonary toxicity and spontaneous reported Grade 2 dyspnea (3.4% vs. 0.9% [Study 2]) was higher in patients receiving Herceptin and chemotherapy compared with chemotherapy alone.
- The most common pulmonary toxicity was dyspnea (NCI-CTC Grade 2-5: 11.8% vs. 4.6% [Study 1]; NCI-CTC Grade 2-5: 2.4% vs. 0.2% [Study 2]).
- Pneumonitis/pulmonary infiltrates occurred in 0.7% of patients receiving Herceptin compared with 0.3% of those receiving chemotherapy alone. Fatal respiratory failure occurred in 3 patients receiving Herceptin, one as a component of multi-organ system failure, as compared to 1 patient receiving chemotherapy alone.
- In Study 3, there were 4 cases of interstitial pneumonitis in the one-year Herceptin treatment arm compared to none in the observation arm at a median follow-up duration of 12.6 months.
Metastatic Breast Cancer
- Among women receiving Herceptin for treatment of metastatic breast cancer, the incidence of pulmonary toxicity was also increased.
- Pulmonary adverse events have been reported in the post-marketing experience as part of the symptom complex of infusion reactions.
- Pulmonary events include
- In 4 randomized, controlled clinical trials, the incidence of thrombotic adverse events was higher in patients receiving Herceptin and chemotherapy compared to chemotherapy alone in three studies (2.6% vs. 1.5% [Study 1], 2.5% and 3.7% vs. 2.2% [Study 4] and 2.1% vs. 0% [Study 5]).
- Among women receiving adjuvant therapy for breast cancer, the incidence of NCI-CTC Grade 2-5 diarrhea (6.7% vs. 5.4% [Study 1]) and of NCI-CTC Grade 3-5 diarrhea (2.2% vs. 0% [Study 2]), and of Grade 1-4 diarrhea (7% vs. 1% [Study 3; one-year Herceptin treatment at 12.6 months median duration of follow-up]) were higher in patients receiving Herceptin as compared to controls.
- In Study 4, the incidence of Grade 3-4 diarrhea was higher [5.7% AC-TH, 5.5% TCH vs. 3.0% AC-T] and of Grade 1-4 was higher [51% AC-TH, 63% TCH vs. 43% AC-T] among women receiving Herceptin.
- Of patients receiving Herceptin as a single agent for the treatment of metastatic breast cancer, 25% experienced diarrhea.
- An increased incidence of diarrhea was observed in patients receiving Herceptin in combination with chemotherapy for treatment of metastatic breast cancer.
- In Study 7 (metastatic gastric cancer) on the Herceptin-containing arm as compared to the chemotherapy alone arm the incidence of renal impairment was 18% compared to 14.5%.
- Severe (Grade 3/4) renal failure was 2.7% on the Herceptin-containing arm compared to 1.7% on the chemotherapy only arm.
- Treatment discontinuation for renal insufficiency/failure was 2% on the Herceptin-containing arm and 0.3% on the chemotherapy only arm.
- In the post-marketing setting, rare cases of nephrotic syndrome with pathologic evidence of glomerulopathy have been reported.
- The time to onset ranged from 4 months to approximately 18 months from initiation of Herceptin therapy.
- Pathologic findings included
- membranous glomerulonephritis,
- focal glomerulosclerosis, and
- fibrillary glomerulonephritis.
- Complications included
- volume overload and
- congestive heart failure.
- As with all therapeutic proteins, there is a potential for immunogenicity.
- Among 903 women with metastatic breast cancer, human anti-human antibody (HAHA) to Herceptin was detected in one patient using an enzyme-linked immunosorbent assay (ELISA). This patient did not experience an allergic reaction.
- Samples for assessment of HAHA were not collected in studies of adjuvant breast cancer.
- The incidence of antibody formation is highly dependent on the sensitivity and the specificity of the assay.
- Additionally, the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors including
- assay methodology,
- sample handling,
- timing of sample collection,
- concomitant medications, and
- underlying disease.
- For these reasons, comparison of the incidence of antibodies to Herceptin with the incidence of antibodies to other products may be misleading.
The following adverse reactions have been identified during post-approval use of Herceptin. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- Infusion reaction
- Oligohydramnios or oligohydramnios sequence, including pulmonary hypoplasia, skeletal abnormalities, and neonatal death
- Immune thrombocytopenia
- Tumor lysis syndrome (TLS): Cases of possible TLS have been reported in patients treated with Herceptin. Patients with significant tumor burden (e.g. bulky metastases) may be at a higher risk. Patients could present with hyperuricemia, hyperphosphatemia, and acute renal failure which may represent possible TLS. Providers should consider additional monitoring and/or treatment as clinically indicated.
What drugs interact with Herceptin (trastuzumab)?
- Patients who receive anthracycline after stopping Herceptin may be at increased risk of cardiac dysfunction because of trastuzumab's long washout period based on population PK analysis.
- If possible, physicians should avoid anthracycline-based therapy for up to 7 months after stopping Herceptin.
- If anthracyclines are used, the patient's cardiac function should be monitored carefully.
Herceptin (trastuzumab) is a monoclonal antibody that is part of a chemotherapy regimen that is used to prevent recurrence of breast cancer, and for the treatment of breast cancer that has spread beyond the breast (metastasized). Common side effects of Herceptin include diarrhea, prickling or burning sensation in the skin, upper respiratory or a catheter-related infection, increased cough, nausea and vomiting, rash, infusion-related reactions including mild to moderate chills and/or fever, insomnia, weight loss, inflammation of the mouth and lips, shortness of breath, distortion of taste, fatigue, pain, cough, and dizziness. Herceptin can cause fetal harm when administered to pregnant women and should not be administered during pregnancy. It is unknown if Herceptin is excreted in breast milk.
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Related Disease Conditions
Breast Cancer in Men
Second Source WebMD Medical Reference
Male Breast Cancer
Male breast cancer accounts for 1% of all breast cancers, and most cases are found in men between the ages of 60 and 70. A man's risk of developing breast cancer is one in 1,000. Signs and symptoms include a firm mass located below the nipple and skin changes around the nipple, including puckering, redness or scaling, retraction and ulceration of the nipple. Treatment depends upon staging and the health of the patient.
Breast cancer is an invasive tumor that develops in the mammary gland. Breast cancer is detected via mammograms, breast self-examination (BSE), biopsy, and specialized testing on breast cancer tissue. Treatment of breast cancer may involve surgery, radiation, hormone therapy, chemotherapy, and targeted therapy. Breast cancer risk may be lowered by managing controllable risk factors. What you should know about breast cancer Breast cancer is the most common cancer among American women. One in every eight women in the United States develops breast cancer. There are many types of breast cancer that differ in their capability of spreading (metastasize) to other body tissues. The causes of breast cancer are unknown, although medical professionals have identified a number of risk factors. There are 11 common types of breast cancer and 4 uncommon types of breast cancer. Breast cancer early signs and symptoms include a lump in the breast or armpit, bloody nipple discharge, inverted nipple, orange-peel texture or dimpling of the breast's skin (peau d'orange), breast pain or sore nipple, swollen lymph nodes in the neck or armpit, and a change in the size or shape of the breast or nipple. Breast cancer can also be symptom free, which makes following national screening recommendations an important practice. Breast cancer is diagnosed during a physical exam, by a self-exam of the breasts, mammography, ultrasound testing, and biopsy. Treatment of breast cancer depends on the type of cancer and its stage (0-IV) and may involve surgery, radiation, or chemotherapy.
Triple-Negative Breast Cancer
Triple-negative breast cancer is more common in Hispanic and African-American women. Signs and symptoms include a lump in the armpit or breast, nipple discharge and inversion, and changes in the breast's skin. Treatment may incorporate surgery, chemotherapy, and radiation therapy.
Can Fibroadenomas Turn Into Breast Cancer?
A fibroadenoma is the most common type of benign, non-cancerous lump of the breast. Although it is rare, complex fibroadenomas and phyllodes tumors have a chance to develop into malignant breast cancer.
Inflammatory Breast Cancer
Inflammatory breast cancer is an accelerated form of breast cancer that is not usually detected by mammogram or ultrasound. Symptoms of inflammatory breast cancer include pain in the breast, skin change in the breast area, bruise on the breast,sudden swelling of the breast, nipple retraction or discharge, and swelling of the lymph nodes.
Breast Cancer Prevention
Lifestyle changes, a healthy antioxidant-rich diet, exercise, and weight reduction can help reduce a woman's risk of developing breast cancer. It's important to be aware of how risk factors such as family history, lifestyle factors, breast conditions, radiation therapy, and hormonal factors may influence your chances of developing breast cancer. Mammography and breast self-examinations are crucial steps in breast cancer prevention.
Breast Cancer and Coping With Stress
Being diagnosed with breast cancer is stressful. Learning relaxation techniques, exercising, eating well, getting adequate sleep, receiving psychotherapy, and maintaining a positive attitude can help you cope. Creating documents, such as an advance directive, living will, and durable power of attorney will outline your wishes in the event that you are no longer able to make decisions regarding your care.
Breast Cancer and Lymphedema
Lymphedema is a common chronic, debilitating condition in which excess fluid called lymph collects in tissues and causes swelling in them. It is common after a mastectomy, lumpectomy or breast cancer surgery and radiation therapy.
Breast Cancer Recurrence
Breast cancer most often recurs within the first 3-5 years after the initial treatment. Changes in the look, feel, or appearance of the breast may indicate breast cancer recurrence. Factors related to recurrence include tumor size, tumor grade, hormone receptor status, lymph node involvement, and oncogene expression. Check out the center below for more medical references on breast cancer, including multimedia (slideshows, images, and quizzes), related diseases, treatment, diagnosis, medications, and prevention or wellness.
How Long After Breast Cancer Can You Get Lymphedema?
Breast cancer means a disease in which the cells of your breast abnormally grow out of control. It commonly occurs in women than in men. There are different types of breast cancer depending on the type of cells that turned cancerous (grow wildly).
Breast Cancer Stages
Breast cancer staging is the determination of the extent and spread of cancer. An individual's health care team uses stages to summarize the extent of cancer in a standardized way that is recognized by all health care providers. They use this staging to determine the treatment most appropriate for the type of cancer. Cancer staging helps to determine the prognosis, or outlook, of cancer, including rates of recurrence and survival rates.
Are There Any Clinical Trials for Breast Cancer?
Breast cancer is the second most common cancer among American women. Around 250,000 women and 2,300 men are diagnosed with breast cancer each year in the United States. Each year, breast cancer kills around 42000 women and 510 men in the United States.
HER2-Positive Breast Cancer
In about 10%-20% of breast cancers, the cancer cells test positive for HER2, sometimes referred to as the HER2/neu protein. HER2 is a growth-promoting protein located on the surface of some cancer cells. HER2-positive breast cancers tend to grow more rapidly and spread more aggressively than breast cancers that are HER2-negative. Doctors do not know what specifically causes some breast cancers to express this protein while others do not.
Breast Cancer Early Warning Signs and Symptoms
In most cases, there are no early warning signs of breast cancer. Breast cancer may not produce any early symptoms, and in many cases, it is first discovered on screening mammography. The most common sign of breast cancer is a new lump or mass in the breast.
What Is Usually the First Sign of Breast Cancer?
A lump in the breast or in the armpits is often the first sign of breast cancer. This may be felt while in the shower. There may or may not be changes in the structure of the breast. Other early signs include changes in breast skin, breast pain and others.
Breast Cancer Treatment
Breast cancer treatments depend upon the type of breast cancer that is present as well as the stage (extent of spread) of the tumor. Treatment for early breast cancer typically involves surgery to remove the tumor. After surgery, medical professionals may administer radiation therapy, chemotherapy, or targeted therapy.
What Is the Breast Cancer BRCA Gene Test?
BRCA genes (BRCA 1 and 2, when normal, repair damaged DNA) are among the genetic mutations linked to breast cancer, ovarian cancer, and other cancers when mutated. Every woman with a BRCA mutation is at high risk for breast cancer, irrespective of whether she has a family history of breast cancer or not. By age 80, a woman with a BRCA mutation has about an 80% chance of developing breast cancer. BRCA1 and BRCA2 gene mutations also increase the risk of ovarian cancer, by 54% and 23%, respectively.
What Questions Should I Ask My Doctor About Breast Cancer?
A diagnosis of breast cancer can be overwhelming, so it's important to write down all your questions before meeting with your doctor.
What Should I Know About Breast Cancer?
Breast cancer is the most common non-skin cancer of American women, but it can also occur in men. Every year in the U.S., there are over 266,000 new diagnoses of breast cancer. A woman has a risk of one in eight for developing breast cancer at some point during her lifetime.
Breast Cancer Treatment by Stage
Treatment of breast cancer depends upon the stage of the cancer at the time of diagnosis. Some of the various treatments include: hormone therapy, radiation therapy, surgery, chemotherapy, HER2-targeted therapy, neoadjuvant therapy, and adjuvant therapy.
What Are The Five Warning Signs Of Breast Cancer?
The majority of breast cancer patients first seek diagnosis because of a lump on the breast. This is one of the five warning signs of breast cancer. Others include changes in the nipple, changes in the breast skin and other symptoms.
What Are the Four Types of Breast Cancer?
The four most common types of breast cancer are ductal carcinoma in situ, lobular carcinoma in situ, invasive ductal carcinoma, invasive lobular carcinoma. The designations are based on the locations of the tumors, whether they have spread and where they have spread to.
Breast Cancer in Young Women
About 5% of cases of breast cancer occur in women under the age of 40 years old. Some risk factors for breast cancer in young women include a personal history of breast cancer or breast disease, family history of breast cancer, prior radiation therapy, and the presence of BRCA1/BRCA2 gene mutations. Breast self-exams, clinical breast exams, and screening mammograms may help detect breast cancer. Treatment may include surgery, chemotherapy, radiation, and hormone therapy.
Breast Cancer Clinical Trials
Breast cancer clinical trials are research programs designed to evaluate new medical treatments, drugs, or devices for the treatment of breast cancer. Clinical trials are designed to test the safety and efficacy of new treatments as well as assess potential side effects. Clinical trials also compare new treatment to existing treatments to determine if it's any better. There are many important questions to ask your doctor before taking part in a breast cancer clinical trial.
Breast Cancer During Pregnancy
Breast cancer occurs in about 1 in every 1,000 pregnant women. Treatment of breast cancer during pregnancy involves surgery, but it is very difficult to protect the baby from the dangerous effects of radiation and chemotherapy. It can be an agonizing to decide whether or not to undergo breast cancer treatment while one is pregnant.
Breast Cancer Growth Rate
The available evidence suggests that breast cancer may begin to grow around 10 years before it is detected. However, the time for development differs from tumor to tumor.
How Can You Detect Breast Cancer Early?
Breast cancer develops from the cells of the breasts and can spread to other parts of the body (metastasis). It is one of the most common cancers diagnosed in women in the United States. A lump in the breast or armpit is often the first sign. Treatment success depends largely on early detection.
What Is the Newest Treatment for Breast Cancer?
Targeted therapies are a newer form of breast cancer treatment. They can be used alone or along with other therapies. Targeted therapies directly target cancer cells or specific processes that contribute to the growth of cancer cells. Target therapy often has fewer side effects.
Genetic Testing: Families With Breast Cancer
Breast cancer can be a killer and the decision to get tested to see if a patient is prone to the disease should be discussed with a doctor -- particularly if the woman has a history of breast cancer in her family. Genetic testing can only tell so much about breast cancer risk, however.
Treatment & Diagnosis
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- Breast Cancer, Metastatic: Treatment Goals and Therapy Options -- Harold J. Burstein, MD
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- How Many Breast Cancer Deaths Are there Each Year?
- Where Can Breast Cancer Spread To?
- Why Is Breast Cancer More Common in Females than Males?
- How Much Breast Cancer is Genetic?
- How Long Can Breast Cancer Patients Live?
- Who Does Breast Cancer Affect?
- How Does Breast Cancer Form?
- How Many Breast Cancer Stages Are There?
- Facts on Breast Cancer Causes, Risk Factors, and Types
- Breast Cancer Symptoms and Signs
- Breast Cancer Detection
- Breast Cancer Treatment
Medications & Supplements
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.