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	Tamoxifen for breast cancer prevention does not benefit most women
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	Breast Cancer
	- Introduction - Causes - Clinical Picture - Screening - Diagnosis - Pathology - Staging - Treatment

Stage 0

1. Lobular carcinoma in situ (LCIS)

Lobular carcinoma in situ. Presently, treatment options include close follow-up, participation in a chemoprevention trial, tamoxifen (Nolvadex), or bilateral total mastectomy with or without reconstruction. At present, the decision for a given treatment will depend upon the patient’s individual risk profile after careful counseling.

2. Ductal carcinoma in situ (DCIS)

Ductal carcinoma in situ (DCIS). Breast-conservation surgery, followed by radiation therapy to the intact breast, is now considered the standard treatment for patients with DCIS.

Axillary lymph nodes

Routine axillary lymph node evacuation is not indicated in the treatment of DCIS since the incidence of positive lymph nodes after axillary lymph node dissection for DCIS is 1%-2%.

 Factors associated with an increased risk of axillary metastasis with a diagnosis of DCIS are

1. Extensive DCIS requiring mastectomy

2. Suspicion of microinvasion

3. DCIS associated with a palpable mass

4. Evidence of lymphovascular permeation or invasion seen on review of the slides.

These factors likely are associated with unknown (nondiagnosed) invasive disease and may benefit from sentinel lymph node dissection.

Adjuvant radiotherapy

A surgical margin of 1 mm has been associated with a 43% chance of having residual disease at the time of re-excision. When a surgical margin of 10 mm (which may not be practical due to cosmetic reasons) can be obtained, there is an extremely low rate of recurrence (4%), and radiotherapy to the breast may not be necessary.

Adjuvant tamoxifen therapy

Adjuvant tamoxifen therapy was shown to benefit women with DCIS in a recent NSABP trial (NSABP-24) in which the tamoxifen group had fewer breast cancer events than those in the placebo group.

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Stage I & II

1. Conservative surgery

Breast-conserving surgery followed by radiation therapy to the intact breast is now considered a standard treatment for the majority of patients with stage I or II invasive breast cancer.

Technique

The extent of breast conservation is debatable. Techniques for breast conservation include: lumpectomy, segmental mastectomy, quadrantectomy & others all of which have a similar in outcome. Quadrantectomy is used by some as it has good safety margin (the radical form of conservative surgery).

A consensus statement on breast-conserving therapy issued by the National Cancer Institute (NCI) recommended that the breast cancer be completely excised with negative surgical margins and that a level I-II axillary lymph node dissection be performed. The patient should subsequently be treated with adjuvant breast irradiation. This should be followed by radiation as part of the 1ry therapy.

Benefits

• Multiple studies have demonstrated that patients with stage I breast cancer who are treated with either breast-conservation therapy (lumpectomy and radiation therapy) or modified radical mastectomy have similar disease-free and overall survival rates.

Contraindications to conservative surgery:

1. Tumor is more than 5cm in size.
2. Diffuse malignant or indeterminate appearing microcalcifications on mammogram.
3. Contraindication to proper cosmesis.
4. Prior breast irradiation or contraindication to radiation.
5. Persistantly positive surgical margins.
6. 1st or 2nd trimester pregnancy.
7. Multicentricity.
8. Intraduct & retroareolar tumors are relative contraindications.
9. History of collagen vascular disease (interfering with healing).

Axillary lymph node surgery following breast conservation

The role of axillary lymph node surgery is controversial when breast conservation is the aim of therapy. Currently, axillary evaluation is recommended in this setting. In these cases sentinel node dissection is recommended when feasible.

The ability to identify the sentinel node can reach as high as 97% when both blue dye and Tc-99m sulfur colloid are used together.

Adjuvant radiation therapy following breast conservation

Breast conservation should be followed by radiation as part of the 1ry therapy.

For patients who undergo axillary dissection and are found to have negative nodes, regional nodal irradiation is no longer routinely employed. For patients with positive nodes, radiation therapy to the supraclavicular fossa and/or internal mammary chain may be considered on an individualized basis.

2. Mastectomy

Patients who are not candidates for breast conservation or are not interested in breast conservation are offered mastectomy.

Adjuvant radiotherapy after mastectomy

Available data suggest that in patients with the following criteria the risk of locoregional failure remains significantly high enough to consider postmastectomy radiation therapy.

• Positive postmastectomy margins

• Primary tumors > 5 cm

• Involvement of 4 or more lymph nodes at the time of mastectomy

Even with the use of high-dose chemotherapy, locoregional failure is a significant problem in these patients without the use of postmastectomy irradiation.

3. Adjuvant chemotherapy

Systemic therapy is indicated only for invasive (infiltrating) breast cancers larger than 1cm in size (in smaller tumors there is a very low risk of recurrence <10%).

The sequence of systemic therapy and definitive radiation therapy in women treated with breast-conserving surgery is a subject of continued clinical research. The use of concomitant chemotherapy and irradiation is not recommended due to the radiomimetic effects of chemotherapy and the potential for increased locoregional toxicity.

Delaying chemotherapy up to 8-10 weeks after surgery does not appear to have a negative impact on the development of metastasis or survival.

Common regimens

• CMF (Bonadonna regimen) and its variants (CMF day 21 and CMF day 28).

• CMF-P (In which prednisone 40mg/m2 from day 1 to day 14).

• AC

• FAC

• TAC

• CAF

• AC --> TAC

• FEC (CEF)

The role of the taxanes, ie, paclitaxel and docetaxel (Taxotere), in adjuvant therapy is being investigated in clinical trials.

Benefit:

1. For all women under 50 years of age at randomization, combination chemotherapy improved 10-year survival from 71% to 78% for those with node-negative disease (an absolute benefit of 7%), and from 42% to 53% for those with node-positive disease (an absolute benefit of 11%).

2. For women 50 to 69 years of age at randomization, combination chemotherapy improved 10-year survival from 67% to 69% for those with node-negative disease (an absolute gain of 2%), and from 46% to 49% for those with node-positive disease (an absolute gain of 3%).

4. Adjuvant hormonal therapy

Hormonal therapy with tamoxifen (20 mg PO qd for 5 years) has been shown to be of value in women ≥ 50 years of age with estrogen- and/or progesterone-receptor–positive tumors as shown in the (ATAC trial).

Benefit:

The most recent meta-analysis, which included information on 37,000 women in 55 trials of adjuvant tamoxifen, was published in 1998. In this analysis, the benefit of tamoxifen was found to be restricted to women with ER-positive or ER-unknown breast tumors.

• In these women, the 10-year proportional reductions in recurrence and mortality associated with 5 years of use were 47% and 26%, respectively.

• An additional observed benefit was an approximately 50% decrease in the incidence of contralateral breast cancer in patients receiving tamoxifen, regardless of the ER status of the primary tumor.

The benefit of tamoxifen is independent of menstrual status. Long-term follow-up from the NSABP conclusively demonstrates that there is no benefit to continuing tamoxifen therapy beyond 5 years.

Stage III (Locally advanced disease)

The optimal treatment for patients with locally advanced breast cancer has yet
to be defined, due to the heterogeneity of this group (stage IIIA and IIIB, M1 supraclavicular nodes).

Neoadjuvant chemotherapy

Neoadjuvant therapy with cytotoxic drugs permits in vivo chemosensitivity testing, can downstage locally advanced disease and render it operable, and may allow breast-conservation surgery to be performed.

Types of neoadjuvant chemotherapy regimens

Preoperative chemotherapy regimens reported to result in high response rates (partial and complete responses) include:

• CAF

• FAC

• CMF

• CMFVP

Combination chemotherapy with an anthracycline-based regimen FAC or AC is used most often. Recently published data suggest that the AT regimen of Adriamycin and docetaxel
(Taxotere) given concomitantly may produce equivalently high response rates.

Although not yet definitive, recent data indicate that enhancing dose density may increase the pathologic complete response rate for women with locally advanced disease.

Benefit:

• Neoadjuvant chemotherapy results in complete response rates ranging in about 25% and partial response rates (≥ 50% reduction in bidimensionally measurable disease) in 50% of cases, with total response rates in about 90%.

Patients with large lesions are more likely to have partial responses. Pathologic complete responses do occur and are more likely to be seen in patients with smaller tumors.

Radiation therapy

Radiation therapy remains an integral component of the management of patients with locally advanced breast cancer.

Operable cases: For patients with operable breast cancer undergoing mastectomy, radiation therapy to the chest wall and/or regional lymph nodes (to a total dose of 5,000-6,000 cGy) is usually employed.

Inoperable cases: For patients whose disease is considered to be inoperable, radiation therapy may be integrated into the management plan prior to surgery.

Multimodality treatment plan

A multimodality approach for locally advanced breast cancer (stage IIIA and IIIB, M1 supraclavicular nodes) consists of

• 4 cycles of neoadjuvant chemotherapy (FAC)

• Followed by surgery for responders / by radiotherapy then surgery for those who do not respond.

• After surgery adjuvant treatment is given in the form of chemotherapy, radiotherapy (unless used in downstaging) and hormonal therapy in those with receptor positive tumors.

Benefit: This approach has been shown to result in the following benefits:

• Stage IIIA disease - 84% 5-year survival rate of

• Stage IIIB disease - 44% 5- year survival rate

• Inflammatory breast cancer - 35%-50% 5-year survival rates

Stage IV (Metastatic disease)

Patients with metastatic cancer can be divided into two groups: those with stage IV disease at presentation and those who develop metastases after primary treatment. They can be divided into low and high risk groups based on the biologic aggressiveness of the disease.

Low-risk patients

The low-risk group includes

• Patients who develop metastatic disease after a long disease-free interval (i.e. a long disease-free interval from primary breast cancer diagnosis to presentation with metastasis),

• those whose tumors are positive for hormone receptors (estrogen and progesterone),

• those with bone-only disease, and

• those without extensive visceral organ involvement.

Hormone therapy in stage IV

First-line hormonal therapy

These drugs aim at reducing the levels of estrogen hormones in hormone receptor positive cancers. First line hormonal therapy consists of an aromatase inhibitor or tamoxifen, with careful serial assessment of clinical and disease responses. Hormone therapy may be associated with a “flare” response, a temporary worsening of signs and symptoms of disease within the first few weeks of treatment. This response generally means clinical benefit will follow. 

Benefits

• Overall response rates is 40% for ER positive tumors

• Complete remission occurs in about 13% in ER positive tumors

• Prolonged disease stability (including minor responses) was achieved in an additional 20 to 30% of patients during hormonal therapy. Stable disease for longer than 6 months is associated with survival durations similar to those of patients who achieve a partial or complete response with endocrine therapy.

Second-line hormonal agents

The most commonly used second-line hormonal agents had been progestational drugs, such as megestrol acetate. Recent randomized trials have indicated that the aromatase inhibitors are equally effective for palliation of metastatic disease, have less toxicity, and may provide a survival advantage compared with megestrol acetate. Therefore, they are the drugs of choice for second-line therapy following tamoxifen administration.

• Anastrozole (Arimidex)
• Letrozole (Femara)
• Fulvestrant (Faslodex)
• Exemestane (Aromasin)

Tamoxifen may also be considered as second-line therapy for patients initially treated with an aromatase inhibitor.

Hormonal therapy continues until evidence of disease progression or drug related toxicity precludes further therapy with the same agent. If a partial or complete response to the first hormonal treatment is documented at the time of disease progression, a second hormonal agent may provide further palliation of symptoms and avoid the initiation of systemic chemotherapy. However, subsequent hormonal responses tend to be of shorter duration, and, ultimately, the disease will become refractory to hormonal treatment.

Cytotoxic agents

Hormone-refractory disease can be treated with systemic cytotoxic therapy.

Combination chemotherapy

• FAC
• Paclitaxel
• TAC (docetaxel, doxorubicin [Adriamycin], cyclophosphamide), or docetaxel may be used in this situation.

Benefits: see below.

Intermediate- or high-risk patients include

• Patients with rapidly progressive disease
• Patients with visceral involvement
• Disease shown to be refractory to hormonal manipulation by a prior therapeutic trial.

Combination chemotherapy in stage IV

Anthracycline-containing combinations are preferred for these patients.

• FAC
• Newer combinations of doxorubicin and a taxane are gaining favor for use in patients who have not received > 450 mg/m2 of an anthracycline and whose relapse has occurred more than 12 months after the completion of adjuvant therapy.

Benefits:

• Between 50 and 75% of patients with metastatic breast cancer have responses to first-line chemotherapy.

• Only 15 to 20% of patients will achieve a complete remission, and most of those patients will develop progressive disease within the subsequent 5 years.

• Anthracycline-based combinations appear to be more effective than CMF and CMFVP in several randomized trials, producing not only higher overall and complete remission rates but, in some studies, significant prolongation of survival as well (about 10% of all complete remissions achieved with anthracycline containing regimens last more than 10 years).

Single agents in stage IV

• Vinblastine (Velban)
• Mitomycin (Mutamycin)
• Thiotepa

• Vinorelbine (Navelbine): Vinorelbine has an objective response rates ranging from 40 to 50% in first-line and 20 to 35% in second-line therapy; however, it has not gained FDA approval, although it is widely used for the treatment of advanced breast cancer.

• Gemcitabine (Gemzar): This agent was approved by the FDA for the treatment of pancreatic cancer, even though its efficacy against breast cancer is substantially higher. Gemcitabine produces responses in about 40% of patients with untreated metastatic breast cancer and in 20 to 30% of those with previous exposure to chemotherapy, including anthracycline-refractory tumors.

• Paclitaxel: One of the most active agents is paclitaxel. Both taxanes have significant antitumor activity in this group of patients with anthracycline-resistant breast cancer, with reported overall response rates of up to 57% and median survival ranging up to 10 months.

• Docetaxel, approved by the FDA for anthracycline-resistant locally advanced or metastatic breast cancer, has demonstrated overall response rates of 41% in doxorubicin-resistant disease. It has been shown to be superior to mitomycin/ vinblastine in patients whose disease progressed after an anthracycline-based chemotherapy regimen. Docetaxel as a single agent produces objective responses in up to 60% of patients with metastatic breast cancer previously unexposed to chemotherapy.

• Capecitabine (Xeloda): has been shown to have substantial antitumor effect in patients whose disease has recurred or progressed after prior anthracycline chemotherapy or after taxane therapy. Prolonged survival, limited toxicity, and response in visceral as well as soft tissue disease add to the benefit of capecitabine.

Benefits:

• 40 to 50% of previously untreated patients with metastatic breast cancer achieve an objective regression after single-agent anthracycline therapy.
• Mitoxantrone and the alkylating agents produce partial or complete responses in 30 to 40% of patients, whereas the other drugs are estimated to have a 20 to 30% response rate.

Trastuzumab (Herceptin)

Trastuzumab is a humanized monoclonal antibody to the HER-2/neu protein, has been approved for use as a single agent in second- and third-line therapy for metastatic breast cancer and in combination with paclitaxel as first-line therapy in this setting.

Benefit:

• The combination of trastuzumab with chemotherapy yields a 45% overall response rate, as compared with a 29% rate with chemotherapy alone. Recent data has shown a superior median overall survival with chemotherapy plus trastuzumab compared with chemotherapy alone (25.4 vs 20.9 months).

• In a multicenter phase II trial of docetaxel, carboplatin / cisplatin, and trastuzumab (TCH) in HER2-positive advanced breast cancer overall responses were observed in 80% of patients receiving cisplatin 60% in those receiving carboplatin. Median times to progression were 10 months for those receiving cisplatin and 13 months in those receiving the carboplatin regimen. Toxicities were mainly hematologic in the carboplatin regimen in the form of grade III and IV thrombocytopenia, neutropenia (with or without fever). In the cisplatin regimen toxicities were mainly non-hematologic and in the form of alopecia, asthenia, GIT toxicities, renal, ototoxicity and neurotoxicity.

Pegram MD, Pienkowski T, Northfelt DW, Eiermann W, Patel R, Fumoleau P, et al. Results of two open-label, multicenter phase II studies of docetaxel, platinum salts, and trastuzumab in HER2-positive advanced breast cancer. J Natl Cancer Inst 2004;96:759–69.

Chemotherapy regimens for breast cancer

Bone metastasis

Surgery for bone metastasis

If x-ray shows a metastatic lesion is in a long bone with cortical destruction, particularly the femur or humerus, pathologic fracture must be prevented if possible. Generally this will require local irradiation and internal fixation with or without systemic therapy.

If the patient presents with or develops a pathologic fracture, internal fixation followed by radiotherapy is a most effective approach, assuming the patient can undergo the operative procedure.

Spinal metastases represent a more difficult problem. Cord compression, nerve root compression, and leptomeningeal metastases can develop. Depending on the results of myelography, CT myelography, or MRI and the patient's status and short-term prognosis, decompressive laminectomy followed by radiotherapy or radiotherapy alone may be selected.

Patients with spinal cord compression who have progressive symptoms during irradiation, disease recurrence after irradiation or who require diagnosis are candidates for surgery. Patients who present with spinal instability often require internal fixation.

Radiation therapy for bone metastasis

External-beam radiotherapy has become a mainstay in the palliative treatment of metastatic bone disease.

1. Postoperative radiotherapy: Postoperative radiotherapy is used after fixation of impending and pathologic fractures and after decompression and stabilization of the spine. When surgery is planned, radiation should be delivered postoperatively to the entire surgical area.

Benefits:

• Only 3% of patients treated with surgery and radiotherapy developed loosening of prostheses or hardware requiring revision surgery, compared to 15% of patients treated with surgery alone. In addition, return to a higher level of function was seen in the combined modality group. 

2. Spinal metastatic disease: Indications for surgery include spinal instability, pathologic fracture with structural canal compromise, circumferential epidural tumor, occult primary tumor, and radioresistant tumors. In spinal metastatic disease, the earlier the diagnosis is made and treatment is initiated, the better the outcome. Radiotherapy should be the first-line therapy when no surgical indication is present.

Among those with spinal metastatic disease, 94% of patients who have the ability to walk maintain their ambulatory status after radiotherapy, whereas ambulation is restored in 60% with motor weakness and 11% with paraplegia at presentation.

3. Palliative radiotherapy:

• Pathologic fractures heal in 35% of patients treated with radiotherapy and nonoperative management.

• Palliative radiotherapy has been shown to provide some relief in 80% to 90% of patients and complete relief in 50% to 85% of patients with localized skeletal disease.

• Before palliative radiotherapy, the bone must be assessed for risk of fracture and the need for surgery. In one study, 13% of long bone and 6% of spinal sites fractured after radiotherapy.

Adjunctive bisphosphonate therapy

Multiple published reports have now confirmed the benefit of bisphosphonates, such as IV pamidronate disodium (Aredia) or zoledronic acid (Zometa), as an adjunct to chemotherapy and hormonal therapy for metastatic breast cancer with osteolytic disease of bone. A significant reduction in skeleton-related events, including bone pain, pathologic fracture, and the need for radiation therapy to bone, occurs in patients treated with chemotherapy and pamidronate disodium for metastatic disease.

Systemic therapy

For breast carcinoma, treatment options are determined by estrogen and progesterone receptor status. In the literature, significant tumor shrinkage with endocrine therapy is 30% to 65%.36 In one study among patients with only bone metastases who were treated with a multiagent regimen (5-fluorouracil, doxorubicin, and cyclophosphamide), complete response rate was 7% and partial response rate was 52%, and an additional 32% experienced stabilization of disease.36 Another large multicenter study evaluated the use of various endocrine agents (megestrol acetate, tamoxifen, aminoglutethimide, dexamethasone, hydrocortisone, and fluoxymesterone) in a placebo arm against pamidronate. A partial response was seen in 21% and a stabilization of disease was seen in an additional 32%.37

If bone metastases are not complicated by pathologic fracture or do not involve the spinal cord or nerve roots, treatment is dictated by symptoms, the risk of pathologic fracture, and the potential for effective systemic therapy. Breast cancer can be effectively palliated using therapies that include castration or treatment with hormones or hormone antagonists. Chemotherapy will often be effective. If the bone metastases are diffuse, palliative radiotherapy may be impractical. In such cases, use of effective oral analgesics will provide effective palliation. If there are a limited number of painful metastatic lesions, radiotherapy delivered to those sites can dramatically alleviate pain and allow the patient to function with less or no analgesics.

Lung metastasis

Lung metastases are preferentially treated with chemotherapy for tumors with a high degree of chemosensitivity. Breast cancer metastasis may respond to hormonal suppression, cytotoxic agents, and molecular targeted therapies.

Also, the lung metastasis is usually coincidental to the discovery of widespread metastatic disease. Significant prognostic factors were a complete resection and a disease-free interval of at least 36 months.

Solitary lesions can be resected with good results, but this represents fewer than 1% of all patients with metastatic breast cancer.

• Reported survival rates of 38% after 5 years, 22% after 10 years, and 20% after 15 years.

Liver metastasis

Breast cancer metastasis may respond to hormonal suppression, cytotoxic agents, and molecular targeted therapies.

Actuarial 5-year survival after resection of clinically isolated hepatic metastases in breast cancer patients is reported between 9% and 18%. Based on the typical systemic pattern of recurrence in patients with advanced breast cancer, this approach must be considered palliative in nature with little expectation of long-term disease control.

Brain metastasis

The median survival time for breast cancer patients with untreated brain metastases is 4 weeks, and can be increased to 4-6 months with whole-brain radiotherapy and stereotactic radiosurgery, or up to 16 months if solitary metastases can be removed surgically.

Corticosteroids and antiseizure medication should be given when indicated.

Radiation therapy

Irradiation remains an integral component of the management of metastatic breast carcinoma.

• In metastatic bony disease (in addition to bisphosphonates).
• Unresectable central nervous system metastases
• Bronchial obstruction
• Painful/fungating breast or chest wall lesions
• Following surgery for decompression of intracranial or spinal cord metastases and following fixation of pathologic fractures

Surgery in metastatic disease

The role of surgery at this point is generally palliative.

• Spinal cord compression
  Patients with spinal cord compression who have progressive symptoms during irradiation, disease recurrence after irradiation, or spinal instability or who require diagnosis are candidates for surgery.
• Solitary brain metastasis
  Patients with a long disease-free interval and solitary brain metastasis may be candidates for resection. Evidence suggests an improved disease-free survival, overall survival, and quality of life in this subset of patients when treated with surgery combined with postoperative cranial irradiation, as compared with radiation therapy alone.
• Bone metastasis
  Pathologic (or impending) fractures may require orthopedic surgery.
• Chest wall resection
  Fungating/ painful breast lesions may require palliative surgical resection. It is extremely rare for a patient with distant metastatic disease to be a candidate for chest wall resection; however, patients with symptomatic recurrence of disease in the chest wall who have limited distant disease and a life expectancy of > 12 months may be appropriate candidates.
• Isolated lung metastases
  The curative benefit of surgery in the treatment of metastatic disease to the lungs or liver is not proven, but, in highly selected cases, surgery may be beneficial.
• Pleural or pericardial effusions
  Symptomatic pleural or pericardial effusions not controlled by other means.

Recurrent breast cancer

Locoregional recurrence of breast cancer can be diagnosed by surgical biopsy or FNA cytology. Whichever modality is appropriate, material should be sent for hormone-receptor studies, since there is only an 80% concordance in hormone-receptor status between the primary tumor and recurrent disease.

Recurrence after breast conservation

Most patients whose disease recurs after conservative treatment for DCIS can be treated with salvage mastectomy. The optimal treatment of a local or regional recurrence after mastectomy has yet to be defined. Locoregional recurrences are associated with initial nodal status and primary tumor size. Appropriate treatment may result in long-term control of locoregional disease.

Recurrent disease in the chest wall after mastectomy

In general, patients who develop minimal recurrent disease in the chest wall after a long disease-free interval may be treated by excision alone, although this approach is controversial and may not be ideal. Locoregional control obtained by radiation therapy alone is related to the volume of residual disease and may not be durable. When possible, disease recurring in the chest wall or
axillary nodes should be resected and radiation therapy should be delivered to aid in local control.

Adjuvant systemic therapy for locoregional recurrence

These data suggest that women whose tumors recur in the ipsilateral breast / regional lymph nodes within the first few years following the original diagnosis may be considered for adjuvant systemic therapy. Given the lack of prospective, randomized data, specific treatment recommendations for these women remain highly individualized.

Adjuvant hormonal therapy in recurrence

Benefits: A recently reported randomized trial demonstrated a disease-free survival benefit with the use of adjuvant tamoxifen following radiation therapy at the time of postmastectomy recurrence of disease in the chest wall in patients with estrogen-receptor–positive tumors.

The 5-year disease-free survival rate was increased from 36% to 59%, and median disease free survival was prolonged by > 4.5 years.

Adjuvant cytotoxic chemotherapy in recurrence

Patients with estrogen-receptor–negative tumors and aggressive locoregional recurrences may also be considered for systemic cytotoxic chemotherapy, given their relatively poor prognosis and the high rate of metastasis.

Follow up

During the months subsequent to therapy patient follow up is usually required every 6 months or every year depending on the risk of breast recurrence. A thorough examination is done aiming primarily at the detection of breast cancer in the opposite breast (due to a slightly increased incidence of contralateral breast cancer).

* Examination should include: bilateral breast & axillary exam in addition to supraclavicular lymph node enlargement and liver examination for enlargement and tenderness. A mammogram is requested annually. In cases that have undergone conservative surgery mammographic examination is recommended every 6 months initially then annually.
A chest x-ray, bone scan (sensitive but not specific) and abdominal sonography is requested as dictated by a patients complaints or the results of the examination.

Warning signs that should alert the physician during an examination:

1. Bony pains accompanied by tenderness
2. Cough or dyspnoea
3. Right hypochondrial pain
4. Neurological manifestations
5. Abnormal CBC (bone marrow infiltration).
6. Edema of arm + pain / parasthesia (possibly an early sign of recurrence).
7. Patients on Tamoxifen may complain of uterine bleeding (endometrial carcinoma) or DVT.
8. Patients on Anthracyclines may complain of manifestations of heart failure.

Prognosis and survival

Memory Aid for breast cancer survival:

The 50% cutoff point is at stage IIIA (50% survive 5yrs, 40% survive 10 years).
From that point add or reduce 10 - 15% with each subsequent or previous stage.

References

Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists' Collaborative Group. Lancet 351(9114): 1451-1467, 1998.

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