prepared by Dr.kucha

1. Case Study Breast Cancer
Nilesh Kucha

2. • G. A., a 37 year old female, married, G1P1 came in for consult due
to a right breast mass.
• HPI:
6 months PTC, the patient felt a 1x1 cm mass over the upper outer
quadrant of her right breast. It was movable and non-tender. No consult
was done. She noted gradual enlargement of the same mass but was non-
tender. One month PTC, she noted skin dimpling on her right breast.
Persistence of the above symptoms with now accompanying tenderness
on the right breast prompted her to seek consult.
• Personal History
Non-smoker, non-alcoholic drinker, with regular monthly menstruation,
G1P1
• Family History:
Aunt died of breast cancer, father has HTN & DM

3. QUESTION 1: What will be your diagnostic
tests/procedures for this patient ?
80% of all breast lumps are not cancer. But if
breast cancer is caught early, your chances of
survival are very good. Some tests that are used
to get a clear diagnosis for invasive ductal
carcinoma are:
• Mammogram
• Biopsy

4. And why?
• Diagnostic mammography should not be confused with screening
mammography, which is performed after a palpable abnormality has been
detected.
• Diagnostic mammography is aimed at evaluating the rest of the breast
before biopsy is performed or occasionally is part of the triple-test
strategy to exclude immediate biopsy.
• Subtle abnormalities that are first detected by screening mammography
should be evaluated carefully by compression or magnified views.
• These abnormalities include clustered microcalcifications, densities
(especially if spiculated), and new or enlarging architectural distortion. For
some nonpalpable lesions, ultrasound may be helpful either to identify
cysts or to guide biopsy.
• If there is no palpable lesion and detailed mammographic studies are
unequivocally benign, the patient should have routine follow-up
appropriate to the patient's age.

5. In patient..
• Excision biopsy was done which revealed a
3x2.5 cm mass with biopsy reading of invasive
ductal carcinoma, Nottingham histologic grade
III. Right Modified Radical Mastectomy was
done and the histopathologic result showed
no residual tumor, 2/12 axillary lymph nodes
positive for tumor, with lymphovascular
invasion. Resection margins are negative for
tumor.

6. • breasts are a common site of potentially fatal
malignancy in women and because they frequently
provide clues to underlying systemic diseases in both
men and women, examination of the breast is an
essential part of the physical examination
• Women should be trained in breast self-examination
(BSE). Although breast cancer in men is unusual,
unilateral lesions should be evaluated in the same
manner as in women, with the recognition that
gynecomastia in men can sometimes begin unilaterally
and is often asymmetri

7. • Virtually all breast cancer is diagnosed by
biopsy of a nodule detected either on a
mammogram or by palpation. Algorithms have
been developed to enhance the likelihood of
diagnosing breast cancer and reduce the
frequency of unnecessary biopsy

9. The Palpable Breast Mass
• Women should be strongly encouraged to examine their breasts
monthly
• The nipple and areolae should be inspected, and an attempt should
be made to elicit nipple discharge. All regional lymph node groups
should be examined, and any lesions should be measured.
• Physical examination alone cannot exclude malignancy. Lesions
with certain features are more likely to be cancerous (hard,
irregular, tethered or fixed, or painless lesions).
• A negative mammogram in the presence of a persistent lump in the
breast does not exclude malignancy. Palpable lesions require
additional diagnostic procedures including biopsy.

10. • In premenopausal women, lesions that are
either equivocal or nonsuspicious on physical
examination should be reexamined in 2–4
weeks, during the follicular phase of the
menstrual cycle. Days 5–7 of the cycle are the
best time for breast examination.

11. EVALUATION OF BREAST MASSES

12. • A dominant mass in a postmenopausal woman or a
dominant mass that persists through a menstrual cycle
in a premenopausal woman should be aspirated by
fine-needle biopsy or referred to a surgeon.
• If nonbloody fluid is aspirated, the diagnosis (cyst) and
therapy have been accomplished together.
• Solid lesions that are persistent, recurrent, complex, or
bloody cysts require mammography and biopsy,
although in selected patients the so-called triple
diagnostic techniques (palpation, mammography,
aspiration) can be used to avoid biopsy.

14. • Ultrasound can be used in place of fine-needle
aspiration to distinguish cysts from solid
lesions.
• Not all solid masses are detected by
ultrasound; thus, a palpable mass that is not
visualized on ultrasound must be presumed to
be solid.

15. What is your management plan for
the patient?
• Neoadjuvant chemotherapy should be considered in
the initial management of all patients with locally
advanced stage III breast cancer. Surgical therapy for
women
• with stage III disease is usually a modified radical
mastectomy, followed by adjuvant radiation therapy.
Chemotherapy is used to maximize distant disease-free
survival, whereas radiation therapy is used to maximize
local-regional disease-free survival. In selected patients
with stage IIIA cancer, neoadjuvant (preoperative)
chemotherapy can reduce the size of the primary
cancer and permit breast-conserving surgery.

16. Surgical and radiation
• Breast-conserving treatments, consisting of the
removal of the primary tumor by some form of
lumpectomy with or without irradiating the breast,
result in a survival that is as good as (or slightly
superior to) that after extensive surgical procedures,
such as mastectomy or modified radical mastectomy,
with or without further irradiation.
• Postlumpectomy breast irradiation greatly reduces the
risk of recurrence in the breast. While breast
conservation is associated with a possibility of
recurrence in the breast, 10-year survival is at least as
good as that after more radical surgery.

17. • Postoperative radiation to regional nodes
following mastectomy is also associated with
an improvement in survival. Since radiation
therapy can also reduce the rate of local or
regional recurrence, it should be strongly
considered following mastectomy for women
with high-risk primary tumors (i.e., T2 in size,
positive margins, positive nodes).

18. • At present, nearly one-third of women in the United States are
managed by lumpectomy. Breast-conserving surgery is not suitable
for all patients: it is not generally suitable for tumors >5 cm (or for
smaller tumors if the breast is small), for tumors involving the
nipple areola complex, for tumors with extensive intraductal
disease involving multiple quadrants of the breast, for women with
a history of collagen-vascular disease, and for women who either
do not have the motivation for breast conservation or do not have
convenient access to radiation therapy. However, these groups
probably do not account for more than one-third of patients who
are treated with mastectomy. Thus, a great many women still
undergo mastectomy who could safely avoid this procedure and
probably would if appropriately counseled

19. Both axillary lymph node involvement and
involvement of vascular or lymphatic channels
by metastatic tumor in the breast are associated
with a higher risk of relapse in the breast but are
not contraindications to breast-conserving
treatment.

20. • Adjuvant therapy is the use of systemic therapies in
patients whose known disease has received local
therapy but who are at risk of relapse. Selection of
appropriate adjuvant chemotherapy or hormone
therapy is highly controversial in some situations.
Meta-analyses have helped to define broad limits for
therapy but do not help in choosing optimal regimens
or in choosing a regimen for certain subgroups of
patients. A summary of recommendations is shown in
Table 86-3. In general, premenopausal women for
whom any form of adjuvant systemic therapy is
indicated should receive multidrug chemotherapy

22. Chemotherapy
• Unlike many other epithelial malignancies, breast cancer responds to
multiple chemotherapeutic agents, including anthracyclines, alkylating
agents, taxanes, and antimetabolites. Multiple combinations of these
agents have been found to improve response rates somewhat, but they
have had little effect on duration of response or survival. The choice
among multidrug combinations frequently depends on whether adjuvant
chemotherapy was administered and, if so, what type. While patients
treated with adjuvant regimens such as cyclophosphamide, methotrexate,
and fluorouracil (CMF regimens) may subsequently respond to the same
combination in the metastatic disease setting, most oncologists use drugs
to which the patients have not been previously exposed. Once patients
have progressed after combination drug therapy, it is most common to
treat them with single agents. Given the significant toxicity of most drugs,
the use of a single effective agent will minimize toxicity by sparing the
patient exposure to drugs that would be of little value. No method to
select the drugs most efficacious for a given patient has been
demonstrated to be useful.

23. • Most oncologists use either an anthracycline or paclitaxel following failure
with the initial regimen. However, the choice has to be balanced with
individual needs. One randomized study has suggested docetaxel may be
superior to paclitaxel. A nanoparticle formulation of paclitaxel (abraxane)
has also shown promise.
• The use of a humanized antibody to erbB2 [trastuzumab (Herceptin)]
combined with paclitaxel can improve response rate and survival for
women whose metastatic tumors overexpress erbB2. The magnitude of
the survival extension is modest in patients with metastatic disease.
Similarly, the use of bevacizumab (avastin) has improved the response rate
and response duration to paclitaxel. Objective responses in previously
treated patients may also be seen with gemcitabine, capecitabine,
navelbine, and oral etoposide

24. QUESTION 3: What other tests do you plan to request ? INCLUDE
ADDITIONAL IMMUNOHISTOPATHOLOGICAL & LABORATORY REQUESTS FOR
STAGING SYSTEM
• The clinical stage of breast cancer is determined
primarily through physical examination of the skin,
breast tissue, and regional lymph nodes (axillary,
supraclavicular, and cervical). However, clinical
determination of axillary lymph node metastases has
an accuracy of only 33%.
• Mammography, chest radiography, and intraoperative
findings (primary tumor size, chest wall invasion) also
provide necessary staging information. Pathologic
stage combines the findings from pathologic
examination of the resected primary breast cancer and
axillary or other regional lymph nodes

25. ImmunoHistoChemistry
• IHC, or ImmunoHistoChemistry, is a special
staining process performed on fresh or frozen
breast cancer tissue removed during biopsy.
IHC is used to show whether or not the cancer
cells have HER2 receptors and/or hormone
receptors on their surface. This information
plays a critical role in treatment planning.

26. IHC for HER2 testing
• IHC is the most commonly used test to see if a tumor
has too much of the HER2 receptor protein on the
surface of the cancer cells. With too many receptors,
the cells receive too many growth signals.
• The IHC test gives a score of 0 to 3+ that indicates the
amount of HER2 receptor protein on the cells in a
sample of breast cancer tissue. If the tissue scores 0 to
1+, it’s called “HER2 negative.” If it scores 2+ or 3+, it’s
called “HER2 positive.” If the results are between 1 and
2, they're considered borderline.

27. Blood Marker Tests
• Examples of markers include:
• CA 15.3: used to find breast and ovarian cancers
• TRU-QUANT and CA 27.29: may mean that breast cancer is present
• CA125: may signal ovarian cancer, ovarian cancer recurrence, and
breast cancer recurrence
• CEA (carcinoembryonic antigen): a marker for the presence of
colon, lung, and liver cancers. This marker may be used to
determine if the breast cancer has traveled to other areas of the
body.
• Circulating tumor cells: cells that break off from the cancer and
move into the blood stream. High circulating tumor cell counts may
indicate that the cancer is growing. The CellSearch test has been
approved by the U.S. Food and Drug Administration to monitor
circulating tumor cells in women diagnosed with metastatic breast
cancer.

28. Biomarkers
• Breast cancer biomarkers are of several types.
Risk factor biomarkers are those associated with
increased cancer risk.
• These include familial clustering and inherited
germline abnormalities, proliferative breast
disease with atypia, and mammographic
densities.
• Exposure biomarkers are a subset of risk factors
that include measures of carcinogen exposure
such as DNA adducts.

29. • These biomarkers are used as endpoints in
short-term chemoprevention trials and
include histologic changes, indices of
proliferation, and genetic alterations leading
to cancer.

31. QUESTION 4 : DISCUSS PROGNOSTIC & PREDICTIVE
FACTORS IN BREAST CANCER
• The most important prognostic variables are provided
by tumor staging.
• The size of the tumor and the status of the axillary
lymph nodes provide reasonably accurate information
on the likelihood of tumor relapse.
• The relation of pathologic stage to 5-year survival is
shown in Table . For most women, the need for
adjuvant therapy can be readily defined on this basis
alone. In the absence of lymph node involvement,
involvement of microvessels (either capillaries or
lymphatic channels) in tumors is nearly equivalent to
lymph node involvement

33. • Estrogen and progesterone receptor status are of
prognostic significance. Tumors that lack either or both of
these receptors are more likely to recur than tumors that
have them.
• Several measures of tumor growth rate correlate with early
relapse. S-phase analysis using flow cytometry is the most
accurate measure. Indirect S-phase assessments using
antigens associated with the cell cycle, such as PCNA (Ki67),
are also valuable.
• Histologic classification of the tumor has also been used as
a prognostic factor. Tumors with a poor nuclear grade have
a higher risk of recurrence than tumors with a good nuclear
grade.

34. • Molecular changes in the tumor are also useful. Tumors that
overexpress erbB2 (HER-2/neu) or have a mutated p53 gene have a
worse prognosis. Particular interest has centered on erbB2
overexpression as measured by histochemistry or by fluorescence
in situ hybridization. Tumors that overexpress erbB2 are more likely
to respond to higher doses of doxorubicin-containing regimens and
predict those tumors that will respond to HER-2/neu antibodies
(trastuzumab) (herceptin) and a Her-2/neu kinase inhibitor.
• To grow, tumors must generate a neovasculature . The presence of
more microvessels in a tumor, particularly when localized in so-
called "hot spots," is associated with a worse prognosis. This may
assume even greater significance in light of blood vessel–targeting
therapies such as bevacizumab (avastin).

35. QUESTION 5: DISCUSS SCREENING TESTS,
SURVEILLANCE & HORMONAL TREATMENT
• Breast cancer is virtually unique among the
epithelial tumors in adults in that screening (in
the form of annual mammography) improves
survival.
• Meta-analysis examining outcomes from every
randomized trial of mammography conclusively
shows a 25–30% reduction in the chance of dying
from breast cancer with annual screening after
age 50; the data for women between ages 40 and
50 are almost as positive.

36. • While controversy continues to surround the
assessment of screening mammography, the
preponderance of data strongly supports the
benefits of screening mammography..

37. • the profound drop in breast cancer mortality
seen over the past decade is unlikely to be solely
attributable to improvements in therapy.
• It seems prudent to recommend annual
mammography for women past the age of 40.
Although no randomized study of BSE has ever
shown any improvement in survival, its major
benefit is identification of tumors appropriate for
conservative local therapy.

38. • Better mammographic technology, including
digitized mammography, routine use of
magnified views, and greater skill in
mammographic interpretation, combined with
newer diagnostic techniques (MRI, magnetic
resonance spectroscopy, positron emission
tomography, etc.) may make it possible to
identify breast cancers even more reliably and
earlier.

39. • Screening by any technique other than
mammography is not indicated; however,
younger women who are BRCA-1 or BRCA-2
carriers may benefit from MRI screening
where the higher sensitivity may outweigh the
loss of specificity

40. • Normal breast tissue is estrogen-dependent.
Both primary and metastatic breast cancer
may retain this phenotype. The best means of
ascertaining whether a breast cancer is
hormone-dependent is through analysis of
estrogen and progesterone receptor levels on
the tumor.

41. • The choice of endocrine therapy is usually
determined by toxicity profile and availability.
In most patients, the initial endocrine therapy
should be an aromatase inhibitor rather than
tamoxifen.
• For the subset of women who are ER positive
but also HER-2/neu positive, response rates to
aromatase inhibitors are very substantially
higher than to tamoxifen.

42. • Newer "pure" antiestrogens that are free of
agonistic effects are also in clinical trial. Cases
in which tumors shrink in response to
tamoxifen withdrawal (as well as withdrawal
of pharmacologic doses of estrogens) have
been reported.
• Endogenous estrogen formation may be
blocked by analogues of luteinizing hormone–
releasing hormone in premenopausal women.

43. • Additive endocrine therapies, including
treatment with progestogens, estrogens, and
androgens, may also be tried in patients who
respond to initial endocrine therapy; the
mechanism of action of these latter therapies
is unknown. Patients who respond to one
endocrine therapy have at least a 50% chance
of responding to a second endocrine therapy.

44. • It is not uncommon for patients to respond to
two or three sequential endocrine therapies;
however, combination endocrine therapies do
not appear to be superior to individual
agents, and combinations of chemotherapy
with endocrine therapy are not useful